DOI: 10.1002/chem.201303329
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& N-Heterocyclic Carbene Solvation
How Can a Carbene be Active in an Ionic Liquid? Martin Thomas,[a] Martin Brehm,[b] Oldamur Hollczki,*[a] and Barbara Kirchner*[a]
Abstract: The solvation of the carbene 1-ethyl-3-methylimidazole-2-ylidene in the ionic liquid 1-ethyl-3-methylimidazolium acetate was investigated by ab initio molecular dynamics simulations in order to reveal the interaction between these two highly important classes of materials: Nheterocyclic carbenes with superb catalytic activity and ionic liquids with advantageous properties as solvents and reaction media. In contrast to previously published data on analogous systems, no hydrogen bond is observed between the hypovalent carbon atom and the most acidic ring hydrogen atoms, as these interaction sites of the imidazolium ring are predominantly occupied by the acetate ions. Keeping the carbene away from the ring hydrogen atoms prevents stabilization of this reactive species, and hence any retarding
1. Introduction N-Heterocyclic carbenes (NHCs)[1–5] are prominent organocatalysts[6–9] providing facile routes, for example, stereoselective CC coupling reactions, which are highly important for general synthetic strategies. Among many other possible media, ionic liquids (ILs)[10–12] may be applied as solvents for the corresponding transformations.[13–18] These solvents often possess numerous advantageous properties, which, together with the versatility of NHCs, may give rise to interesting and powerful applications. In the last two decades, it has been shown that hydrogen bonds play a crucial role in both the structures of ILs[19–22] and the chemistry of NHCs.[23–28] The cation of an IL often acts as a strong hydrogen-bond donor, and the anion can serve as an acceptor. These interactions can be directly quantified in terms of the corresponding Kamlet–Taft parameters[29] based on the shift in the IR bands of a dissolved dye. For instance, in the case of the most widely applied 1,3-dialkylimidazolium-based
effect on subsequent reactions, which explains the observed high reactivity of the carbene in acetate-based ionic liquids. Instead, the carbene exhibits a weaker interaction with the methyl group of the imidazolium cation by forming a hitherto unprecedented kind of C···HC hydrogen bond. This unexpected finding not only indicates a novel kind of hydrogen bond for carbenes, but also shows that such interaction sites of the imidazolium cation are not limited to the ring hydrogen atoms. Thus, the results give the solute–solvent interactions within ionic liquids a new perspective, and provide a further, albeit weak, site of interaction to tune in order to achieve the desired environment for any dissolved active ingredient.
ILs, hydrogen bonds can be formed by all of the hydrogen atoms on the positively charged ring.[19–22] The presence of these interactions has been suggested to have remarkable effects on the physicochemical properties.[30–32] NHCs generally possess high basicities,[33–36] which makes them very strong hydrogen-bond acceptors. Accordingly, several hydrogen-bonded structures with various donor molecules have been characterized,[23, 24, 27] including that with water.[28] Consistent with the aforementioned donor–acceptor properties, a C···HC-type hydrogen bond between a 1,3-dialkylimidazolium cation and the corresponding carbene derivative was observed in the 1990s[23] (1 in Figure 1), and a similar interaction between two NHC molecules through one of the remaining ring hydrogen atoms was subsequently reported[25] (2 in Figure 1). Considering all of this information, it is reasonable to
[a] M. Thomas, Dr. O. Hollczki, Prof. Dr. B. Kirchner Mulliken Center for Theoretical Chemistry Rheinische Friedrich-Wilhelms-Universitt Bonn Beringstr. 4,D-53115 Bonn (Germany) E-mail: [email protected] [email protected] [b] M. Brehm Wilhelm-Ostwald-Institut fr Physikalische und Theoretische Chemie Linnstr. 2,D-04103 Leipzig (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201303329. Chem. Eur. J. 2014, 20, 1622 – 1629
Figure 1. Hydrogen-bonded carbene complexes characterized by X-ray crystallography (top),[23, 25] and proton transfer between the 1-ethyl-3-methylimidazolium cation and acetate (bottom).[27]
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Full Paper assume that an NHC dissolved in a 1,3-dialkylimidazoliumbased IL will be incorporated into the hydrogen-bonding network. Since these hydrogen bonds are often rather strong, the hydrogen-bonded complexes can be low-energy intermediates,[27, 28, 37] modifying the reactivity of the NHC by decelerating the subsequent reaction steps.[28, 37, 38] Accordingly, it has been observed that in the IL 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide an NHC-catalyzed CC coupling reaction yielding g-butyrolactones proceeds with significantly lower rates and selectivities compared to those measured in tetrahydrofuran,[17] most likely as a result of the aforementioned hydrogen-bonding interactions between the IL and the NHC.[17] This matter becomes particularly intriguing regarding the chemical similarities between these two kinds of materials: the cation of imidazolium-based ILs can be converted into an NHC, namely 1,3-dialkylimidazole-2-ylidene, by a single deprotonation.[33–36] This connection not only provides a facile route to NHCs in general, but by choosing a sufficiently basic counteranion for the IL itself (e.g., acetate or hydrogencarbonate) a latent carbene activity may be achieved for the corresponding solvent.[27, 39–45] This intrinsic functionality has been directly observed in the gas phase by spectroscopic methods,[27] showing that the equilibrium depicted in Figure 1 is slightly shifted towards the carbene-containing hydrogen-bonded structure (4), which can even dissociate under lower pressures. In the liquid phase, however, the charge network of the IL solution[46, 47] suppresses the formation of the neutral NHC and acetic acid, making the ionic imidazolium acetate (3) the more stable isomer. Consequently, the NHC has not yet been directly observed in an IL by any experimental method. Nevertheless, indirect evidence for the accessibility of the carbene has been provided by trapping reactions with different chalcogens, benzaldehyde,[39] and carbon dioxide.[40] It is important to point out that the IL 1-ethyl-3-methylimidazolium acetate has been shown to be highly active as an organocatalyst in benzoin condensation and in hydroacylation,[41] despite the aforementioned observation that NHC organocatalysts in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide showed almost no reactivity.[17] Moreover, the possible formation of highly stable hydrogen bonds between the accessible carbene and the imidazolium cation (see above) could presumably stabilize the carbene to an observable extent. These seemingly contradictory notions show that a detailed characterization of the interactions between these two classes of compounds is highly important, since their proper assessment may help to influence or even tune the reactivity and selectivity of the catalysts in ILs in the aforementioned reactions, which are of great synthetic and technological value. Moreover, exploring the interactions stabilizing the carbene in IL media may be of direct value for the applications of these ILs with latent carbene activity by defining the properties that may influence the accessibility of the carbene. Thus, in this study, we aimed to understand how NHCs are situated in ILs. For this purpose, ab initio molecular dynamics (AIMD) simulations have been performed on 1-ethyl-3-methylimidazolium acetate with a 1-ethyl-3-methylimidazole-2-ylidene Chem. Eur. J. 2014, 20, 1622 – 1629
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molecule and an acetic acid molecule (see Figure 1) dissolved in the system. We show that in this case an unprecedented interaction with the methyl group of the IL cation may be established, in agreement with previous ab initio calculations showing remarkable positive charge at this moiety.[48] This also indicates that, in general, alkyl moieties[49] may not be as immune to hydrogen bonding as previously thought.
2. Results and Discussion 2.1 Computational details A system containing 35 ion pairs of 1-ethyl-3-methylimidazolium acetate and one molecule of 1-ethyl-3-methylimidazole-2ylidene (35P + C) was simulated in a cubic box with a size of 2121.24 pm under periodic boundary conditions (Figure 2). For full details, see the Supporting Information. Since the proton transfer yields an acetic acid molecule (Figure 1), this species was also included. The simulation of the pure ionic liquid containing 36 ion pairs of 1-ethyl-3-methylimidazolium acetate (36P) has been described elsewhere.[42] The AIMD simulations were performed using the CP2K program package[50] with the BLYP functional and Grimme’s dispersion correction D3.[51] The BLYP-D3 dispersion-corrected GGA functional has been shown to provide reasonable results for ionic liquids.[52–54] A time step of 0.5 fs was chosen and the temperature was set at 350 K. The system 35P + C was equilibrated using an individual thermostat for each degree of freedom over a period of 10.4 ps. The production simulation was subsequently run for 63.1 ps. Static calculations were carried out using Turbomole 6.0.[55] Density functional theory was applied with the RI approximation and the B97-D exchange-correlation functional,[56] and a polarized triple-zeta basis set (def2-TZVPP) was used for all atoms.[55] To reduce the number of different conformers, the 1,3-dimethylimidazolium cation was considered, as previous studies have shown that this change of the alkyl side chain does not significantly influence the cation–anion interaction in the gas phase.[27, 28, 49] Topological analysis of the electron density was performed with the AIMAll program package,[57] whereby bond critical points were localized to verify the presence of covalent bonds and to assess their strength according to the electron densities (1BCP) at these points. This approach, together with molecular orbital theory and different population analyses, is suggested to provide valuable information on charged
Figure 2. Representative snapshots of the simulation boxes (cations in blue, anions in red, carbene in green, H(OAc)2 in yellow).
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Figure 3. Atom labeling used throughout this article. (Note that the cation is marked without primes, the carbene with single primes, and the anion with double primes.)
hydrogen-bonded systems,[58] and also on the interactions within IL ion pairs.[19, 49] Since in some recent studies the importance of the electrostatic interactions within IL ion pairs has been emphasized,[59] we also applied electrostatic potential fitted charges (qESP) to compare the ability of the anion and the carbene to interact with the imidazolium cation. Structural analyses of the trajectories were performed using TRAVIS.[60] The atom labeling used in the following discussion is shown in Figure 3. The geometric ring centers of the cation and the carbene are denoted as CoR and CoR’, respectively. 2.2 Interactions through the hydrogen atoms Interactions through the ring hydrogen atoms of the cation and the carbene were compared by the radial distribution functions (RDFs) of these atoms and the acetate oxygen atoms; see Figure 4. As previously observed for the pure IL,[42] the curves for the cation exhibit distinct maxima with a higher peak at 195 pm for H2 and somewhat lower peaks at 212 pm corresponding to H4 and H5; see Figure 4, upper panel. This clearly indicates that the ring hydrogen atoms of the cation are all strong interaction sites; see the Supporting Information for further details. The differences in peak heights and locations show that the more acidic H2[61] has a slightly stronger interaction with the anions. In the case of the carbene, this strongly interacting H2 is absent, but the other two RDFs show similarly pronounced peaks at 212 pm and 232 pm, respectively. The slight difference in peak heights between H4’ and H5’ could be due to the finite sampling time. The shift of the maxima to somewhat larger distances indicates that the interaction of the acetate with the carbene is weaker than that with the cation, which can be explained in terms of the differences in total charge. Although the absence of H2 reduces the number of possible interaction sites with the acetate ions, the lone pair of the carbene should allow for hydrogen bonding[23–28] with the cation;[19–22] thus, the carbene should compete with the acetate anion for the ring hydrogen atoms of the cation. By static gasChem. Eur. J. 2014, 20, 1622 – 1629
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Figure 4. Radial distribution functions: a) cation ring hydrogen atoms H2, H4, and H5 as well as carbene ring hydrogen atoms H4’ and H5’ with respect to acetate oxygen atoms O’’; b) cation ring hydrogen atoms H2, H4, and H5 with respect to the carbene C2’ atom; c) cation side-chain hydrogen atoms H6, H7, and H8 with respect to acetate oxygen atoms O’’ and carbene C2’ atom. (The weaker interaction with the H7 atom is due to its higher mobility and hydrophobicity.)
phase calculations, three low minima could be found on the potential energy surface of a single carbene and a cation; see Figure 5. The most stable isomer D1 is analogous to the previously described structure,[23] exhibiting a single C2’···H2C2 hydrogen bond. The stability of this bond is indicated not only by its unusually high dissociation energy (DEdiss = 85 kJ mol1, as compared to 23 kJ mol1 for a water dimer at the same level of theory), but also by the electron density at the corresponding bond critical point (1BCP = 0.0339 a.u., as compared to 0.0248 a.u. between two water molecules). In D2, the hypovalent carbon atom forms two individual hydrogen bonds, apparently interacting with both the H4 atom and the methyl group, which is, therefore, rotated by around 608 compared to its orientation in D1 and D3. The localized bond critical points
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Full Paper 1) peak at around 200 pm in the C2’-H2 RDF corresponds only to a temporary close approach of these two atoms, which move apart again after a few picoseconds (see the Supporting Information). No such approaches were observed for either of the other two ring hydrogen atoms. The lack of strong hydrogen-bonding interactions with the ring hydrogen atoms of the cation is rather unexpected if one considers the aforementioned matching hydrogen-bonding abilities of the solvent and the carbene, which is also well illustrated by the corresponding reported structures 1[23] and 2[25] (Figure 1). Interestingly, this indicates that the presence of the acetate anion prevents the formation of such complexes between the carbene and the cation, and one may deduce that the hypovalent carbon atom of the carbene is free of any interactions in the liquid, which would explain the retention of its high reactivity in the corresponding IL.[41] Figure 5. Dissociation energies as well as hydrogen-bonding distances (in pm) and bond Thus, the question arises whether the hypovalent critical point electron densities (in atomic units) for three optimized structures of the hydrogen-bonded complex between the 1,3-dimethylimidazolium cation and 1,3-dimethylcarbon atom of the carbene exists in a “naked” state imidazole-2-ylidene, and three optimized structures of a single 1,3-dimethylimidazolium in the solution, without forming any interactions with acetate ion pair. the cation. Considering the RDFs between C2’ and the side-chain hydrogen atoms of the cation also support this bifurcated arrangement, showing that the (Figure 4, lower panel), a pronounced peak at a surprisingly two bonds are comparable in strength (1BCP = 0.0199 a.u. and short (200 pm) distance can be observed for those of the 1BCP = 0.0126 a.u. for the ring and the methyl hydrogen atoms, methyl group, in good qualitative accordance with previous respectively). Despite the presence of two stabilizing interactheoretical results[48] showing significant positive charges at tions, the dissociation energy of this structure (DEdiss = these positions. In agreement with the static calculations for D2, this interaction may even possess a well-defined direction72 kJ mol1) is somewhat lower than that of D1. Interestingly, ality, preferring a C2’-H8-C8 angle of about 1808, as also shown however, this structure is more stable than D3 (DEdiss = by the combined distribution function (CDF) in Figure 6. All of 60 kJ mol1), in which there are two interactions with the ring these data clearly suggest the presence of an unprecedented hydrogen atoms. The more bent C2’···H(4,5)-C(4,5) bond in D3 hydrogen bond between the carbene and the methyl group. suggests more strain than that in D2, in agreement with the Furthermore, this interesting finding not only indicates a hitherlower electron densities at the corresponding bond critical to unknown kind of hydrogen-bonding mode for carbenes, points (Figure 5). but also infers that the alkyl chains of imidazolium cations in The high dissociation energies and the relative energies ILs cannot be considered[49] inert in terms of anion–cation infound in the static calculations suggest that the carbene should form a strong hydrogen bond with the imidazolium teractions and hydrogen bonding. cation, preferably through H2. However, comparing the RDFs of the ring hydrogen atoms of the cation and the carbene C2’ to that of the acetate oxygen atoms (Figure 4, middle panel), a rather different picture emerges. While it can be seen that the RDFs for the acetate anion show strong maxima, the RDFs for the hypovalent carbon atom of the carbene show no distinct peaks, from which it can be concluded that this atom does not form any hydrogen bond with the ring hydrogen atoms of the cation. It should be Figure 6. Combined distribution function showing the directionality of hydrogen bonding between the carbene noted here that the small (below and cation’s methyl group: C2’-H8-C8 angle versus the C2’-H8 distance. Chem. Eur. J. 2014, 20, 1622 – 1629
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Full Paper According to the above results, the solvation of the carbene can be rationalized as a competition between the carbene and the acetate anion for the best interaction sites of the cation. Obviously, the higher negative charge at the oxygen atoms of the acetate anion (qOESP = 0.842) compared to the hypovalent 0 carbon atom (qC2 ESP = 0.555) makes a significant difference in the interaction, and therefore the most positively polarized[19, 62] ring hydrogen atoms should show a marked preference for the anions in hydrogen bonding. This is also in accordance with the higher electron densities at the bond critical points (see Figure 5), showing that the acetate is bound to the hydrogen atoms more strongly than the carbene. Also, despite the fact that in the liquid there are 50 % more ring hydrogen atoms than acetate oxygen atoms, one oxygen atom forms multiple interactions,[63] as was found in the 36P simulation: one acetate anion forms hydrogen bonds with an average of 5.4 hydrogen atoms. Considering that there are three ring hydrogen atoms and eight alkyl hydrogen atoms per cation, the acetate anion can almost completely occupy the ring hydrogen sites, leaving the less polar and therefore less competitive alkyl hydrogen atoms for the carbene. This emerging picture of the relatively free carbene explains how this species can retain its potent reactivity in the liquid, and although it is non-observable due to the lack of stabilization, it can still exhibit significant organocatalytic activity. Clearly, using a less basic anion (such as triflate or bis(trifluoromethanesulfonyl)imide) would imply the formation of weaker hydrogen bonds with the ring hydrogen atoms of the cation,[27] which would result in less competitive interactions. This competition at the ring hydrogen atoms has been amply demonstrated in mixtures of ionic liquids:[64, 65] comparing the chloride anion to the thiocyanate anion, it has been found that the former outcompetes the latter in coordinating to H2 of the cation.[64, 65] Therefore, in cases with less basic anions—although the carbene is not formed spontaneously—the presence of structures analogous to 1 should be more feasible; decreasing the catalytic activity of an external carbene catalyst dissolved in such media, as has been observed in the IL 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide.[17] 2.3 Further NHC–solvent interactions Besides the hydrogen-bonding situation, we also characterized further interactions of the carbene with the solvent IL ions. Ring-stacking of the cations through p–p interactions (resulting in a parallel alignment of the relevant rings) has been found to occur in some pure ILs,[66, 67] including neat 1-ethyl-3methylimidazolium acetate.[67, 68] Since electrostatic repulsion is reduced by the lack of positive total charge at the carbene, pstacking with this species could, in principle, be more facilitated. However, the RDFs of the cation and carbene ring centers in Figure 7 and the combined distribution functions in Figure 8 show precisely the opposite trend. As for the pure IL,[68] the cation–cation interaction shows a first small (g(r) < 1) peak at a very short 350 pm distance. This corresponds to a parallel on-top orientation (solid line in Figure 7), indicating the formaChem. Eur. J. 2014, 20, 1622 – 1629
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Figure 7. Radial distribution functions of cation ring centers with respect to cation’s ring center and carbene’s ring center.
tion of weakly bound p–p stacking structures. The carbene– cation ring center distance, however, exhibits a first peak at 550 pm (dashed line in Figure 7). According to the CDF in Figure 8, this corresponds to a much shorter C2’-H8 distance, indicating that these interactions arise from hydrogen bonding with the methyl group of the cation rather than from p–p stacking. Since the hydrogen-bonding interaction is remarkably directional, the C2’-H8-C8 assembly prefers an angle of around 1808 (see Figure 6), the carbene is kept fixed, tilted out of the plane of the coplanar ring stacking alignment. This accounts for the distinct peak in the CoR’-CoR RDF at 550 pm. It is also interesting to note that this directionality keeps the methyl group of the cation in a fairly fixed position (Figure 8; see the Supporting Information for further details on the carbene– cation alignment). As another important general interaction in ILs,[67, 69, 70] dispersion-induced aggregation of the ethyl side chains was considered. This interaction has been observed for the ethyl chains of the present ionic liquid,[68] and in the case of longer alkyl substituents the segregation of these functionalities into nonpolar domains, resulting in a microheterogeneity of the corresponding ILs, has been reported.[69, 70] In the case of two cations, there is a peak in the C7-C7 RDF at 400 pm (see Figure 9), showing some correlation of the ethyl chains of the cations, as has been found in the pure IL.[68] For the carbene, a significantly more pronounced peak at the same distance could be observed. This peak partly corresponds to the interaction with the cation involved in hydrogen bonding with the carbene through the methyl group, but in some cases the side chains of other cations also approach the methyl group of the carbene (see the Supporting Information for further details). Therefore, this increased side-chain clustering can be explained not only in terms of the hydrogen bond between the carbene and the cation, but presumably also on the basis of reduced electrostatic repulsion between the rings. Thus, this observation suggests the possibility that carbene formation may be influenced by choosing longer alkyl substituents on the nitrogen. This would provide neutral domains in the IL that might facilitate carbene formation through introduced larger defects[71] in the ion screening, while also better accommodating the carbene through these increased side-chain interactions.
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Figure 8. Combined distribution functions showing the preferred alignment of the carbene and the cation: a) dependence of CoR’-CoR distance on C2’-H8 distance, b) dependence of H8-C8-N3-C2 dihedral angle on C2’-H8 distance.
Figure 9. Radial distribution functions of cation’s C7 atoms with respect to the other cation’s C7 atom and carbene’s C7’ atom, representing the degree of microheterogeneity.
3. Conclusion The solvation of a 1-ethyl-3-methylimidazole-2-ylidene carbene molecule within the 1-ethyl-3-methylimidazolium acetate ionic liquid was investigated. According to previous experimental data,[23] a strong hydrogen-bonding interaction of the carbene with the ring hydrogen atoms of the imidazolium cation could be expected. Interestingly, it turned out that these positions of the cation are occupied exclusively by the basic acetate Chem. Eur. J. 2014, 20, 1622 – 1629
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anions, excluding the carbene from these interaction sites. Such competition for the ring hydrogen atoms has previously been observed for mixtures of chloride and thiocyanate ILs.[64, 65] Instead, the carbene forms an unexpected C···HC hydrogen bond with the alkyl substituent of the cation. To the best of our knowledge, such a C···HC hydrogen bond has not yet been observed for either NHCs or ILs. Thus, our results point to an unknown bonding mode of carbenes, and also imply that the alkyl side chain of the IL cation is not entirely immune to such interactions, which puts the theory of solute– solvent interactions within ILs into a novel perspective. Therefore, the possibility of such weak hydrogen-bonding interactions with the side chain[49] has to be considered in IL theory and applications, and may also provide a potential site for influencing or tuning the intermolecular interactions between the IL solvent and any given solute. These results also have a direct impact on the overlap of these two great fields of chemistry, namely carbenes and ionic liquids. As has been shown in previous studies,[27, 39–41] in the case of 1,3-dialkylimidazolium-based ILs having basic anions (e.g., acetate), a latent carbene content can be observed, as an anion of sufficiently high proton affinity will abstract a proton from the cation. However, the lack of strong hydrogen bonding between the hypovalent carbon atom of the carbene and the ring hydrogen atoms of the imidazolium cation affects the stability of NHCs in ILs, suppressing the spontaneous proton transfer in imidazolium acetate-based ionic liquids (Figure 1,
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Full Paper below). Therefore, the strong hydrogen-bond-accepting property of the basic anions counteracts their proton-abstracting potential, and even if the latent carbene reactivity is connected to the basicity of the anion, this very property makes the direct (spectroscopic) observation of the presumably transient species more difficult. On the other hand, since the formed (or external) carbene is not stabilized by any such strong hydrogen bonds, it can retain its original reactivity, and can show high (organo)catalytic activity in this IL, as has been shown experimentally.[41] Clearly, the hydrogen-bonding behavior can be different for ILs with less basic anions, in which this competition between the carbene and the anion for the best hydrogen-bonding sites is shifted from one side to the other. Since basicity of the anion is necessary for the spontaneous (or induced)[71] formation of the carbene from the IL, this factor is more pertinent in the case of syntheses employing external NHCs in IL media. Consistent with this, in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide a significant decrease in NHC activity has been observed.[17] In turn, this idea may be used for tuning of the (organo)catalytic activity of carbenes in ionic liquids, namely to facilitate slower reactions by decreasing the hydrogen bonding of the carbene by changing from less basic to more basic anions. Besides this interesting hydrogen-bonding behavior of the investigated system, a lesser degree of importance of ring stacking, and, partly due to the decrease in repulsive electrostatic interaction, some significance of side-chain aggregation has been observed. All of these effects together offer a possible means of tuning the accessibility of the carbene in the present type of ILs, which is, therefore, not limited only to higher or lower basicity of the anion that directly shifts the equilibrium of the proton transfer. The length of the side chain may also be modified, with longer side chains possibly inducing carbene formation through partial offsetting of the charge screening that stabilizes ionic species,[71] and apparently also by accommodating the carbene in these nonpolar domains.
Acknowledgements Financial support by the Alexander von Humboldt Foundation for the postdoctoral stay of O.H. and by the DFG through projects SPP1191, KI768/5-2, and KI768/5-3 is gratefully acknowledged. Keywords: hydrogen bonds · ionic liquids · N-heterocyclic carbenes · reactivity · solvation [1] D. Bourissou, O. Guerret, F. P. Gabbaı¨, G. Bertrand, Chem. Rev. 2000, 100, 39 – 92. [2] F. Hahn, M. Jahnke, Angew. Chem. 2008, 120, 3166 – 3216; Angew. Chem. Int. Ed. 2008, 47, 3122 – 3172. [3] T. Drçge, F. Glorius, Angew. Chem. 2010, 122, 7094 – 7107; Angew. Chem. Int. Ed. 2010, 49, 6940 – 6952. [4] M. Melaimi, M. Soleilhavoup, G. Bertrand, Angew. Chem. 2010, 122, 8992 – 9032; Angew. Chem. Int. Ed. 2010, 49, 8810 – 8849. [5] D. Martin, M. Melaimi, M. Soleilhavoup, G. Bertrand, Organometallics 2011, 30, 5304 – 5313. Chem. Eur. J. 2014, 20, 1622 – 1629
www.chemeurj.org
[6] D. Enders, T. Balensiefer, Acc. Chem. Res. 2004, 37, 534 – 541. [7] D. Enders, O. Niemeier, A. Henseler, Chem. Rev. 2007, 107, 5606 – 5655. [8] N. Marion, S. Dez-Gonzlez, S. Nolan, Angew. Chem. 2007, 119, 3046 – 3058; Angew. Chem. Int. Ed. 2007, 46, 2988 – 3000. [9] J. L. Moore, T. Rovis, in Asymmetric Organocatalysis, Vol. 291 of Top. Curr. Chem. (Ed.: B. List), Springer, Berlin/Heidelberg, 2009, pp. 118 – 144. [10] T. Welton, Chem. Rev. 1999, 99, 2071 – 2084. [11] T. Welton, Coord. Chem. Rev. 2004, 248, 2459 – 2477. [12] J. P. Hallett, T. Welton, Chem. Rev. 2011, 111, 3508 – 3576. [13] E. F. Connor, G. W. Nyce, M. Myers, A. Mçck, J. L. Hedrick, J. Am. Chem. Soc. 2002, 124, 914 – 915. [14] G. W. Nyce, J. A. Lamboy, E. F. Connor, R. M. Waymouth, J. L. Hedrick, Org. Lett. 2002, 4, 3587 – 3590. [15] G. A. Grasa, R. M. Kissling, S. P. Nolan, Org. Lett. 2002, 4, 3583 – 3586. [16] G. A. Grasa, T. Gveli, R. Singh, S. P. Nolan, J. Org. Chem. 2003, 68, 2812 – 2819. [17] M. H. Dunn, M. L. Cole, J. B. Harper, RSC Adv. 2012, 2, 10160 – 10162. [18] M. Feroci, I. Chiarotto, A. Inesi, Curr. Org. Chem. 2013, 17, 204 – 219. [19] P. A. Hunt, B. Kirchner, T. Welton, Chem. Eur. J. 2006, 12, 6762 – 6775. [20] V. Kempter, B. Kirchner, J. Mol. Struct. 2010, 972, 22 – 34. [21] S. B. C. Lehmann, M. Roatsch, M. Schçppke, B. Kirchner, Phys. Chem. Chem. Phys. 2010, 12, 7473 – 7486. [22] I. Skarmoutsos, D. Dellis, R. P. Matthews, T. Welton, P. A. Hunt, J. Phys. Chem. B 2012, 116, 4921 – 4933. [23] A. J. Arduengo III, S. F. Gamper, M. Tamm, J. C. Calabrese, F. Davidson, H. A. Craig, J. Am. Chem. Soc. 1995, 117, 572 – 573. [24] J. A. Cowan, J. A. C. Clyburne, M. G. Davidson, R. L. W. Harris, J. A. K. Howard, P. Kpper, M. A. Leech, S. P. Richards, Angew. Chem. 2002, 114, 1490 – 1492; Angew. Chem. Int. Ed. 2002, 41, 1432 – 1434. [25] L. A. Leites, G. I. Magdanurov, S. S. Bukalov, R. West, Mendeleev Commun. 2008, 18, 14 – 15. [26] S. D. Sarkar, S. Grimme, A. Studer, J. Am. Chem. Soc. 2010, 132, 1190 – 1191. [27] O. Hollczki, D. Gerhard, K. Massone, L. Szarvas, B. Nmeth, T. Veszprmi, L. Nyulszi, New J. Chem. 2010, 34, 3004 – 3009. [28] O. Hollczki, P. Terleczky, D. Szieberth, G. Mourgas, D. Gudat, L. Nyulszi, J. Am. Chem. Soc. 2011, 133, 780 – 789. [29] L. Crowhurst, P. R. Mawdsley, J. M. Perez-Arlandis, P. A. Salter, T. Welton, Phys. Chem. Chem. Phys. 2003, 5, 2790 – 2794. [30] P. A. Hunt, J. Phys. Chem. B 2007, 111, 4844 – 4853. [31] S. Zahn, G. Bruns, J. Thar, B. Kirchner, Phys. Chem. Chem. Phys. 2008, 10, 6921 – 6924. [32] K. Noack, P. S. Schulz, N. Paape, J. Kiefer, P. Wasserscheid, A. Leipertz, Phys. Chem. Chem. Phys. 2010, 12, 14153 – 14161. [33] R. W. Alder, P. R. Allen, S. J. Williams, J. Chem. Soc. Chem. Commun. 1995, 1267 – 1268. [34] Y.-J. Kim, A. Streitweiser, J. Am. Chem. Soc. 2002, 124, 5757. [35] H. Chen, D. R. Justes, R. G. Cooks, Org. Lett. 2005, 7, 3949 – 3952. [36] Y. Chu, H. Deng, J.-P. Cheng, J. Org. Chem. 2007, 72, 7790. [37] O. Hollczki, Z. Kelemen, L. Nyulszi, J. Org. Chem. 2012, 77, 6014 – 6022. [38] Z. Kelemen, O. Hollczki, J. Olh, L. Nyulszi, RSC Adv. 2013, 3, 7970 – 7978. [39] H. Rodrguez, G. Gurau, J. D. Holbrey, R. D. Rogers, Chem. Commun. 2011, 47, 3222 – 3224. [40] G. Gurau, H. Rodrguez, S. P. Kelley, P. Janiczek, R. S. Kalb, R. D. Rogers, Angew. Chem. 2011, 123, 12230 – 12232; Angew. Chem. Int. Ed. 2011, 50, 12024 – 12026. [41] Z. Kelemen, O. Hollczki, J. Nagy, L. Nyulszi, Org. Biomol. Chem. 2011, 9, 5362 – 5364. [42] M. Brehm, H. Weber, A. S. Pensado, A. Stark, B. Kirchner, Phys. Chem. Chem. Phys. 2012, 14, 5030 – 5044. [43] O. Hollczki, L. Nyulszi, of Top. Curr. Chem., Springer, Berlin/Heidelberg, 2013, DOI: 10.1007/128_2012_416. [44] M. Fvre, J. Pinaud, A. Leteneur, Y. Gnanou, J. Vignolle, D. Taton, K. Miqueu, J.-M. Sotiropoulos, J. Am. Chem. Soc. 2012, 134, 6776 – 6784. [45] M. Fvre, P. Coupillaud, K. Miqueu, J.-M. Sotiropoulos, J. Vignolle, D. Taton, J. Org. Chem. 2012, 77, 10135 – 10144. [46] J. P. Hallett, C. L. Liotta, G. Ranieri, T. Welton, J. Org. Chem. 2009, 74, 1864 – 1868.
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Full Paper [47] M. Y. Lui, L. Crowhurst, J. P. Hallett, P. A. Hunt, H. Niedermeyer, T. Welton, Chem. Sci. 2011, 2, 1491 – 1496. [48] S. Tsuzuki, H. Tokuda, K. Hayamizu, M. Watanabe, J. Phys. Chem. B 2005, 109, 16474 – 16481. [49] O. Hollczki, L. Nyulszi, Org. Biomol. Chem. 2011, 9, 2634 – 2640. [50] CP2K developers group, http://www.cp2k.org/. [51] S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010, 132, 154104. [52] S. Zahn, B. Kirchner, J. Phys. Chem. A 2008, 112, 8430 – 8435. [53] A. S. Pensado, M. Brehm, J. Thar, A. P. Seitsonen, B. Kirchner, ChemPhysChem 2012, 13, 1845 – 1853. [54] S. Grimme, W. Hujo, B. Kirchner, Phys. Chem. Chem. Phys. 2012, 14, 4875 – 4883. [55] R. Ahlrichs, M. B r, M. H ser, H. Horn, C. Kçlmel, Chem. Phys. Lett. 1989, 162, 165, Current version: see http://www.turbomole.de. [56] S. Grimme, J. Comput. Chem. 2006, 27, 1787 – 1799. [57] AIMAll (Version 13.11.04), Todd A. Keith, TK Gristmill Software, Overland Park KS, USA, 2013 (http://aim.tkgristmill.com). [58] F. Weinhold, R. A. Klein, Mol. Phys. 2012, 110, 565 – 579. [59] S. Tsuzuki, H. Tokuda, M. Mikami, Phys. Chem. Chem. Phys. 2007, 9, 4780 – 4784. [60] M. Brehm, B. Kirchner, J. Chem. Inf. Model. 2011, 51, 2007 – 2023. [61] R. Tonner, G. Heydenrych, G. Frenking, Chem. Asian J. 2007, 2, 1555 – 1567.
Chem. Eur. J. 2014, 20, 1622 – 1629
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[62] T. Cremer, C. Kolbeck, K. Lovelock, N. Paape, R. Wçlfel, P. Schulz, P. Wasserscheid, H. Weber, J. Thar, B. Kirchner, F. Maier, H.-P. Steinrck, Chem. Eur. J. 2010, 16, 9018 – 9033. [63] A. Stark, M. Brehm, M. Brssel, S. B. C. Lehmann, A. S. Pensado, M. Schçppke, B. Kirchner, Top. Curr. Chem. accepted. [64] M. Brssel, M. Brehm, T. Voigt, B. Kirchner, Phys. Chem. Chem. Phys. 2011, 13, 13617 – 13620. [65] M. Brssel, M. Brehm, A. S. Pensado, F. Malberg, M. Ramzan, A. Stark, B. Kirchner, Phys. Chem. Chem. Phys. 2012, 14, 13204 – 13215. [66] J. S. Wilkes, M. J. Zaworotko, Supramol. Chem. 1993, 1, 191 – 193. [67] H. Weber, O. Hollczki, A. S. Pensado, B. Kirchner, J. Chem. Phys. 2013, 139, 084502. [68] M. Brehm, H. Weber, A. S. Pensado, A. Stark, B. Kirchner, Z. Phys. Chem. 2013, 227, 177 – 204. [69] Y. Wang, G. A. Voth, J. Am. Chem. Soc. 2005, 127, 12192 – 12193. [70] J. N. A. Canongia Lopes, A. A. H. Pdua, J. Phys. Chem. B 2006, 110, 3330 – 3335. [71] O. Hollczki, D. S. Firaha, J. Friedrich, M. Brehm, R. Cybik, M. Wild, A. Stark, B. Kirchner, J. Phys. Chem. B 2013, 117, 5898 – 5907.
Received: August 25, 2013 Revised: November 14, 2013 Published online on December 27, 2013
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& N-Heterocyclic Carbene Solvation
How Can a Carbene be Active in an Ionic Liquid? Martin Thomas,[a] Martin Brehm,[b] Oldamur Hollczki,*[a] and Barbara Kirchner*[a]
Abstract: The solvation of the carbene 1-ethyl-3-methylimidazole-2-ylidene in the ionic liquid 1-ethyl-3-methylimidazolium acetate was investigated by ab initio molecular dynamics simulations in order to reveal the interaction between these two highly important classes of materials: Nheterocyclic carbenes with superb catalytic activity and ionic liquids with advantageous properties as solvents and reaction media. In contrast to previously published data on analogous systems, no hydrogen bond is observed between the hypovalent carbon atom and the most acidic ring hydrogen atoms, as these interaction sites of the imidazolium ring are predominantly occupied by the acetate ions. Keeping the carbene away from the ring hydrogen atoms prevents stabilization of this reactive species, and hence any retarding
1. Introduction N-Heterocyclic carbenes (NHCs)[1–5] are prominent organocatalysts[6–9] providing facile routes, for example, stereoselective CC coupling reactions, which are highly important for general synthetic strategies. Among many other possible media, ionic liquids (ILs)[10–12] may be applied as solvents for the corresponding transformations.[13–18] These solvents often possess numerous advantageous properties, which, together with the versatility of NHCs, may give rise to interesting and powerful applications. In the last two decades, it has been shown that hydrogen bonds play a crucial role in both the structures of ILs[19–22] and the chemistry of NHCs.[23–28] The cation of an IL often acts as a strong hydrogen-bond donor, and the anion can serve as an acceptor. These interactions can be directly quantified in terms of the corresponding Kamlet–Taft parameters[29] based on the shift in the IR bands of a dissolved dye. For instance, in the case of the most widely applied 1,3-dialkylimidazolium-based
effect on subsequent reactions, which explains the observed high reactivity of the carbene in acetate-based ionic liquids. Instead, the carbene exhibits a weaker interaction with the methyl group of the imidazolium cation by forming a hitherto unprecedented kind of C···HC hydrogen bond. This unexpected finding not only indicates a novel kind of hydrogen bond for carbenes, but also shows that such interaction sites of the imidazolium cation are not limited to the ring hydrogen atoms. Thus, the results give the solute–solvent interactions within ionic liquids a new perspective, and provide a further, albeit weak, site of interaction to tune in order to achieve the desired environment for any dissolved active ingredient.
ILs, hydrogen bonds can be formed by all of the hydrogen atoms on the positively charged ring.[19–22] The presence of these interactions has been suggested to have remarkable effects on the physicochemical properties.[30–32] NHCs generally possess high basicities,[33–36] which makes them very strong hydrogen-bond acceptors. Accordingly, several hydrogen-bonded structures with various donor molecules have been characterized,[23, 24, 27] including that with water.[28] Consistent with the aforementioned donor–acceptor properties, a C···HC-type hydrogen bond between a 1,3-dialkylimidazolium cation and the corresponding carbene derivative was observed in the 1990s[23] (1 in Figure 1), and a similar interaction between two NHC molecules through one of the remaining ring hydrogen atoms was subsequently reported[25] (2 in Figure 1). Considering all of this information, it is reasonable to
[a] M. Thomas, Dr. O. Hollczki, Prof. Dr. B. Kirchner Mulliken Center for Theoretical Chemistry Rheinische Friedrich-Wilhelms-Universitt Bonn Beringstr. 4,D-53115 Bonn (Germany) E-mail: [email protected] [email protected] [b] M. Brehm Wilhelm-Ostwald-Institut fr Physikalische und Theoretische Chemie Linnstr. 2,D-04103 Leipzig (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201303329. Chem. Eur. J. 2014, 20, 1622 – 1629
Figure 1. Hydrogen-bonded carbene complexes characterized by X-ray crystallography (top),[23, 25] and proton transfer between the 1-ethyl-3-methylimidazolium cation and acetate (bottom).[27]
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Full Paper assume that an NHC dissolved in a 1,3-dialkylimidazoliumbased IL will be incorporated into the hydrogen-bonding network. Since these hydrogen bonds are often rather strong, the hydrogen-bonded complexes can be low-energy intermediates,[27, 28, 37] modifying the reactivity of the NHC by decelerating the subsequent reaction steps.[28, 37, 38] Accordingly, it has been observed that in the IL 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide an NHC-catalyzed CC coupling reaction yielding g-butyrolactones proceeds with significantly lower rates and selectivities compared to those measured in tetrahydrofuran,[17] most likely as a result of the aforementioned hydrogen-bonding interactions between the IL and the NHC.[17] This matter becomes particularly intriguing regarding the chemical similarities between these two kinds of materials: the cation of imidazolium-based ILs can be converted into an NHC, namely 1,3-dialkylimidazole-2-ylidene, by a single deprotonation.[33–36] This connection not only provides a facile route to NHCs in general, but by choosing a sufficiently basic counteranion for the IL itself (e.g., acetate or hydrogencarbonate) a latent carbene activity may be achieved for the corresponding solvent.[27, 39–45] This intrinsic functionality has been directly observed in the gas phase by spectroscopic methods,[27] showing that the equilibrium depicted in Figure 1 is slightly shifted towards the carbene-containing hydrogen-bonded structure (4), which can even dissociate under lower pressures. In the liquid phase, however, the charge network of the IL solution[46, 47] suppresses the formation of the neutral NHC and acetic acid, making the ionic imidazolium acetate (3) the more stable isomer. Consequently, the NHC has not yet been directly observed in an IL by any experimental method. Nevertheless, indirect evidence for the accessibility of the carbene has been provided by trapping reactions with different chalcogens, benzaldehyde,[39] and carbon dioxide.[40] It is important to point out that the IL 1-ethyl-3-methylimidazolium acetate has been shown to be highly active as an organocatalyst in benzoin condensation and in hydroacylation,[41] despite the aforementioned observation that NHC organocatalysts in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide showed almost no reactivity.[17] Moreover, the possible formation of highly stable hydrogen bonds between the accessible carbene and the imidazolium cation (see above) could presumably stabilize the carbene to an observable extent. These seemingly contradictory notions show that a detailed characterization of the interactions between these two classes of compounds is highly important, since their proper assessment may help to influence or even tune the reactivity and selectivity of the catalysts in ILs in the aforementioned reactions, which are of great synthetic and technological value. Moreover, exploring the interactions stabilizing the carbene in IL media may be of direct value for the applications of these ILs with latent carbene activity by defining the properties that may influence the accessibility of the carbene. Thus, in this study, we aimed to understand how NHCs are situated in ILs. For this purpose, ab initio molecular dynamics (AIMD) simulations have been performed on 1-ethyl-3-methylimidazolium acetate with a 1-ethyl-3-methylimidazole-2-ylidene Chem. Eur. J. 2014, 20, 1622 – 1629
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molecule and an acetic acid molecule (see Figure 1) dissolved in the system. We show that in this case an unprecedented interaction with the methyl group of the IL cation may be established, in agreement with previous ab initio calculations showing remarkable positive charge at this moiety.[48] This also indicates that, in general, alkyl moieties[49] may not be as immune to hydrogen bonding as previously thought.
2. Results and Discussion 2.1 Computational details A system containing 35 ion pairs of 1-ethyl-3-methylimidazolium acetate and one molecule of 1-ethyl-3-methylimidazole-2ylidene (35P + C) was simulated in a cubic box with a size of 2121.24 pm under periodic boundary conditions (Figure 2). For full details, see the Supporting Information. Since the proton transfer yields an acetic acid molecule (Figure 1), this species was also included. The simulation of the pure ionic liquid containing 36 ion pairs of 1-ethyl-3-methylimidazolium acetate (36P) has been described elsewhere.[42] The AIMD simulations were performed using the CP2K program package[50] with the BLYP functional and Grimme’s dispersion correction D3.[51] The BLYP-D3 dispersion-corrected GGA functional has been shown to provide reasonable results for ionic liquids.[52–54] A time step of 0.5 fs was chosen and the temperature was set at 350 K. The system 35P + C was equilibrated using an individual thermostat for each degree of freedom over a period of 10.4 ps. The production simulation was subsequently run for 63.1 ps. Static calculations were carried out using Turbomole 6.0.[55] Density functional theory was applied with the RI approximation and the B97-D exchange-correlation functional,[56] and a polarized triple-zeta basis set (def2-TZVPP) was used for all atoms.[55] To reduce the number of different conformers, the 1,3-dimethylimidazolium cation was considered, as previous studies have shown that this change of the alkyl side chain does not significantly influence the cation–anion interaction in the gas phase.[27, 28, 49] Topological analysis of the electron density was performed with the AIMAll program package,[57] whereby bond critical points were localized to verify the presence of covalent bonds and to assess their strength according to the electron densities (1BCP) at these points. This approach, together with molecular orbital theory and different population analyses, is suggested to provide valuable information on charged
Figure 2. Representative snapshots of the simulation boxes (cations in blue, anions in red, carbene in green, H(OAc)2 in yellow).
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Figure 3. Atom labeling used throughout this article. (Note that the cation is marked without primes, the carbene with single primes, and the anion with double primes.)
hydrogen-bonded systems,[58] and also on the interactions within IL ion pairs.[19, 49] Since in some recent studies the importance of the electrostatic interactions within IL ion pairs has been emphasized,[59] we also applied electrostatic potential fitted charges (qESP) to compare the ability of the anion and the carbene to interact with the imidazolium cation. Structural analyses of the trajectories were performed using TRAVIS.[60] The atom labeling used in the following discussion is shown in Figure 3. The geometric ring centers of the cation and the carbene are denoted as CoR and CoR’, respectively. 2.2 Interactions through the hydrogen atoms Interactions through the ring hydrogen atoms of the cation and the carbene were compared by the radial distribution functions (RDFs) of these atoms and the acetate oxygen atoms; see Figure 4. As previously observed for the pure IL,[42] the curves for the cation exhibit distinct maxima with a higher peak at 195 pm for H2 and somewhat lower peaks at 212 pm corresponding to H4 and H5; see Figure 4, upper panel. This clearly indicates that the ring hydrogen atoms of the cation are all strong interaction sites; see the Supporting Information for further details. The differences in peak heights and locations show that the more acidic H2[61] has a slightly stronger interaction with the anions. In the case of the carbene, this strongly interacting H2 is absent, but the other two RDFs show similarly pronounced peaks at 212 pm and 232 pm, respectively. The slight difference in peak heights between H4’ and H5’ could be due to the finite sampling time. The shift of the maxima to somewhat larger distances indicates that the interaction of the acetate with the carbene is weaker than that with the cation, which can be explained in terms of the differences in total charge. Although the absence of H2 reduces the number of possible interaction sites with the acetate ions, the lone pair of the carbene should allow for hydrogen bonding[23–28] with the cation;[19–22] thus, the carbene should compete with the acetate anion for the ring hydrogen atoms of the cation. By static gasChem. Eur. J. 2014, 20, 1622 – 1629
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Figure 4. Radial distribution functions: a) cation ring hydrogen atoms H2, H4, and H5 as well as carbene ring hydrogen atoms H4’ and H5’ with respect to acetate oxygen atoms O’’; b) cation ring hydrogen atoms H2, H4, and H5 with respect to the carbene C2’ atom; c) cation side-chain hydrogen atoms H6, H7, and H8 with respect to acetate oxygen atoms O’’ and carbene C2’ atom. (The weaker interaction with the H7 atom is due to its higher mobility and hydrophobicity.)
phase calculations, three low minima could be found on the potential energy surface of a single carbene and a cation; see Figure 5. The most stable isomer D1 is analogous to the previously described structure,[23] exhibiting a single C2’···H2C2 hydrogen bond. The stability of this bond is indicated not only by its unusually high dissociation energy (DEdiss = 85 kJ mol1, as compared to 23 kJ mol1 for a water dimer at the same level of theory), but also by the electron density at the corresponding bond critical point (1BCP = 0.0339 a.u., as compared to 0.0248 a.u. between two water molecules). In D2, the hypovalent carbon atom forms two individual hydrogen bonds, apparently interacting with both the H4 atom and the methyl group, which is, therefore, rotated by around 608 compared to its orientation in D1 and D3. The localized bond critical points
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Full Paper 1) peak at around 200 pm in the C2’-H2 RDF corresponds only to a temporary close approach of these two atoms, which move apart again after a few picoseconds (see the Supporting Information). No such approaches were observed for either of the other two ring hydrogen atoms. The lack of strong hydrogen-bonding interactions with the ring hydrogen atoms of the cation is rather unexpected if one considers the aforementioned matching hydrogen-bonding abilities of the solvent and the carbene, which is also well illustrated by the corresponding reported structures 1[23] and 2[25] (Figure 1). Interestingly, this indicates that the presence of the acetate anion prevents the formation of such complexes between the carbene and the cation, and one may deduce that the hypovalent carbon atom of the carbene is free of any interactions in the liquid, which would explain the retention of its high reactivity in the corresponding IL.[41] Figure 5. Dissociation energies as well as hydrogen-bonding distances (in pm) and bond Thus, the question arises whether the hypovalent critical point electron densities (in atomic units) for three optimized structures of the hydrogen-bonded complex between the 1,3-dimethylimidazolium cation and 1,3-dimethylcarbon atom of the carbene exists in a “naked” state imidazole-2-ylidene, and three optimized structures of a single 1,3-dimethylimidazolium in the solution, without forming any interactions with acetate ion pair. the cation. Considering the RDFs between C2’ and the side-chain hydrogen atoms of the cation also support this bifurcated arrangement, showing that the (Figure 4, lower panel), a pronounced peak at a surprisingly two bonds are comparable in strength (1BCP = 0.0199 a.u. and short (200 pm) distance can be observed for those of the 1BCP = 0.0126 a.u. for the ring and the methyl hydrogen atoms, methyl group, in good qualitative accordance with previous respectively). Despite the presence of two stabilizing interactheoretical results[48] showing significant positive charges at tions, the dissociation energy of this structure (DEdiss = these positions. In agreement with the static calculations for D2, this interaction may even possess a well-defined direction72 kJ mol1) is somewhat lower than that of D1. Interestingly, ality, preferring a C2’-H8-C8 angle of about 1808, as also shown however, this structure is more stable than D3 (DEdiss = by the combined distribution function (CDF) in Figure 6. All of 60 kJ mol1), in which there are two interactions with the ring these data clearly suggest the presence of an unprecedented hydrogen atoms. The more bent C2’···H(4,5)-C(4,5) bond in D3 hydrogen bond between the carbene and the methyl group. suggests more strain than that in D2, in agreement with the Furthermore, this interesting finding not only indicates a hitherlower electron densities at the corresponding bond critical to unknown kind of hydrogen-bonding mode for carbenes, points (Figure 5). but also infers that the alkyl chains of imidazolium cations in The high dissociation energies and the relative energies ILs cannot be considered[49] inert in terms of anion–cation infound in the static calculations suggest that the carbene should form a strong hydrogen bond with the imidazolium teractions and hydrogen bonding. cation, preferably through H2. However, comparing the RDFs of the ring hydrogen atoms of the cation and the carbene C2’ to that of the acetate oxygen atoms (Figure 4, middle panel), a rather different picture emerges. While it can be seen that the RDFs for the acetate anion show strong maxima, the RDFs for the hypovalent carbon atom of the carbene show no distinct peaks, from which it can be concluded that this atom does not form any hydrogen bond with the ring hydrogen atoms of the cation. It should be Figure 6. Combined distribution function showing the directionality of hydrogen bonding between the carbene noted here that the small (below and cation’s methyl group: C2’-H8-C8 angle versus the C2’-H8 distance. Chem. Eur. J. 2014, 20, 1622 – 1629
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Full Paper According to the above results, the solvation of the carbene can be rationalized as a competition between the carbene and the acetate anion for the best interaction sites of the cation. Obviously, the higher negative charge at the oxygen atoms of the acetate anion (qOESP = 0.842) compared to the hypovalent 0 carbon atom (qC2 ESP = 0.555) makes a significant difference in the interaction, and therefore the most positively polarized[19, 62] ring hydrogen atoms should show a marked preference for the anions in hydrogen bonding. This is also in accordance with the higher electron densities at the bond critical points (see Figure 5), showing that the acetate is bound to the hydrogen atoms more strongly than the carbene. Also, despite the fact that in the liquid there are 50 % more ring hydrogen atoms than acetate oxygen atoms, one oxygen atom forms multiple interactions,[63] as was found in the 36P simulation: one acetate anion forms hydrogen bonds with an average of 5.4 hydrogen atoms. Considering that there are three ring hydrogen atoms and eight alkyl hydrogen atoms per cation, the acetate anion can almost completely occupy the ring hydrogen sites, leaving the less polar and therefore less competitive alkyl hydrogen atoms for the carbene. This emerging picture of the relatively free carbene explains how this species can retain its potent reactivity in the liquid, and although it is non-observable due to the lack of stabilization, it can still exhibit significant organocatalytic activity. Clearly, using a less basic anion (such as triflate or bis(trifluoromethanesulfonyl)imide) would imply the formation of weaker hydrogen bonds with the ring hydrogen atoms of the cation,[27] which would result in less competitive interactions. This competition at the ring hydrogen atoms has been amply demonstrated in mixtures of ionic liquids:[64, 65] comparing the chloride anion to the thiocyanate anion, it has been found that the former outcompetes the latter in coordinating to H2 of the cation.[64, 65] Therefore, in cases with less basic anions—although the carbene is not formed spontaneously—the presence of structures analogous to 1 should be more feasible; decreasing the catalytic activity of an external carbene catalyst dissolved in such media, as has been observed in the IL 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide.[17] 2.3 Further NHC–solvent interactions Besides the hydrogen-bonding situation, we also characterized further interactions of the carbene with the solvent IL ions. Ring-stacking of the cations through p–p interactions (resulting in a parallel alignment of the relevant rings) has been found to occur in some pure ILs,[66, 67] including neat 1-ethyl-3methylimidazolium acetate.[67, 68] Since electrostatic repulsion is reduced by the lack of positive total charge at the carbene, pstacking with this species could, in principle, be more facilitated. However, the RDFs of the cation and carbene ring centers in Figure 7 and the combined distribution functions in Figure 8 show precisely the opposite trend. As for the pure IL,[68] the cation–cation interaction shows a first small (g(r) < 1) peak at a very short 350 pm distance. This corresponds to a parallel on-top orientation (solid line in Figure 7), indicating the formaChem. Eur. J. 2014, 20, 1622 – 1629
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Figure 7. Radial distribution functions of cation ring centers with respect to cation’s ring center and carbene’s ring center.
tion of weakly bound p–p stacking structures. The carbene– cation ring center distance, however, exhibits a first peak at 550 pm (dashed line in Figure 7). According to the CDF in Figure 8, this corresponds to a much shorter C2’-H8 distance, indicating that these interactions arise from hydrogen bonding with the methyl group of the cation rather than from p–p stacking. Since the hydrogen-bonding interaction is remarkably directional, the C2’-H8-C8 assembly prefers an angle of around 1808 (see Figure 6), the carbene is kept fixed, tilted out of the plane of the coplanar ring stacking alignment. This accounts for the distinct peak in the CoR’-CoR RDF at 550 pm. It is also interesting to note that this directionality keeps the methyl group of the cation in a fairly fixed position (Figure 8; see the Supporting Information for further details on the carbene– cation alignment). As another important general interaction in ILs,[67, 69, 70] dispersion-induced aggregation of the ethyl side chains was considered. This interaction has been observed for the ethyl chains of the present ionic liquid,[68] and in the case of longer alkyl substituents the segregation of these functionalities into nonpolar domains, resulting in a microheterogeneity of the corresponding ILs, has been reported.[69, 70] In the case of two cations, there is a peak in the C7-C7 RDF at 400 pm (see Figure 9), showing some correlation of the ethyl chains of the cations, as has been found in the pure IL.[68] For the carbene, a significantly more pronounced peak at the same distance could be observed. This peak partly corresponds to the interaction with the cation involved in hydrogen bonding with the carbene through the methyl group, but in some cases the side chains of other cations also approach the methyl group of the carbene (see the Supporting Information for further details). Therefore, this increased side-chain clustering can be explained not only in terms of the hydrogen bond between the carbene and the cation, but presumably also on the basis of reduced electrostatic repulsion between the rings. Thus, this observation suggests the possibility that carbene formation may be influenced by choosing longer alkyl substituents on the nitrogen. This would provide neutral domains in the IL that might facilitate carbene formation through introduced larger defects[71] in the ion screening, while also better accommodating the carbene through these increased side-chain interactions.
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Figure 8. Combined distribution functions showing the preferred alignment of the carbene and the cation: a) dependence of CoR’-CoR distance on C2’-H8 distance, b) dependence of H8-C8-N3-C2 dihedral angle on C2’-H8 distance.
Figure 9. Radial distribution functions of cation’s C7 atoms with respect to the other cation’s C7 atom and carbene’s C7’ atom, representing the degree of microheterogeneity.
3. Conclusion The solvation of a 1-ethyl-3-methylimidazole-2-ylidene carbene molecule within the 1-ethyl-3-methylimidazolium acetate ionic liquid was investigated. According to previous experimental data,[23] a strong hydrogen-bonding interaction of the carbene with the ring hydrogen atoms of the imidazolium cation could be expected. Interestingly, it turned out that these positions of the cation are occupied exclusively by the basic acetate Chem. Eur. J. 2014, 20, 1622 – 1629
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anions, excluding the carbene from these interaction sites. Such competition for the ring hydrogen atoms has previously been observed for mixtures of chloride and thiocyanate ILs.[64, 65] Instead, the carbene forms an unexpected C···HC hydrogen bond with the alkyl substituent of the cation. To the best of our knowledge, such a C···HC hydrogen bond has not yet been observed for either NHCs or ILs. Thus, our results point to an unknown bonding mode of carbenes, and also imply that the alkyl side chain of the IL cation is not entirely immune to such interactions, which puts the theory of solute– solvent interactions within ILs into a novel perspective. Therefore, the possibility of such weak hydrogen-bonding interactions with the side chain[49] has to be considered in IL theory and applications, and may also provide a potential site for influencing or tuning the intermolecular interactions between the IL solvent and any given solute. These results also have a direct impact on the overlap of these two great fields of chemistry, namely carbenes and ionic liquids. As has been shown in previous studies,[27, 39–41] in the case of 1,3-dialkylimidazolium-based ILs having basic anions (e.g., acetate), a latent carbene content can be observed, as an anion of sufficiently high proton affinity will abstract a proton from the cation. However, the lack of strong hydrogen bonding between the hypovalent carbon atom of the carbene and the ring hydrogen atoms of the imidazolium cation affects the stability of NHCs in ILs, suppressing the spontaneous proton transfer in imidazolium acetate-based ionic liquids (Figure 1,
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Full Paper below). Therefore, the strong hydrogen-bond-accepting property of the basic anions counteracts their proton-abstracting potential, and even if the latent carbene reactivity is connected to the basicity of the anion, this very property makes the direct (spectroscopic) observation of the presumably transient species more difficult. On the other hand, since the formed (or external) carbene is not stabilized by any such strong hydrogen bonds, it can retain its original reactivity, and can show high (organo)catalytic activity in this IL, as has been shown experimentally.[41] Clearly, the hydrogen-bonding behavior can be different for ILs with less basic anions, in which this competition between the carbene and the anion for the best hydrogen-bonding sites is shifted from one side to the other. Since basicity of the anion is necessary for the spontaneous (or induced)[71] formation of the carbene from the IL, this factor is more pertinent in the case of syntheses employing external NHCs in IL media. Consistent with this, in 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide a significant decrease in NHC activity has been observed.[17] In turn, this idea may be used for tuning of the (organo)catalytic activity of carbenes in ionic liquids, namely to facilitate slower reactions by decreasing the hydrogen bonding of the carbene by changing from less basic to more basic anions. Besides this interesting hydrogen-bonding behavior of the investigated system, a lesser degree of importance of ring stacking, and, partly due to the decrease in repulsive electrostatic interaction, some significance of side-chain aggregation has been observed. All of these effects together offer a possible means of tuning the accessibility of the carbene in the present type of ILs, which is, therefore, not limited only to higher or lower basicity of the anion that directly shifts the equilibrium of the proton transfer. The length of the side chain may also be modified, with longer side chains possibly inducing carbene formation through partial offsetting of the charge screening that stabilizes ionic species,[71] and apparently also by accommodating the carbene in these nonpolar domains.
Acknowledgements Financial support by the Alexander von Humboldt Foundation for the postdoctoral stay of O.H. and by the DFG through projects SPP1191, KI768/5-2, and KI768/5-3 is gratefully acknowledged. Keywords: hydrogen bonds · ionic liquids · N-heterocyclic carbenes · reactivity · solvation [1] D. Bourissou, O. Guerret, F. P. Gabbaı¨, G. Bertrand, Chem. Rev. 2000, 100, 39 – 92. [2] F. Hahn, M. Jahnke, Angew. Chem. 2008, 120, 3166 – 3216; Angew. Chem. Int. Ed. 2008, 47, 3122 – 3172. [3] T. Drçge, F. Glorius, Angew. Chem. 2010, 122, 7094 – 7107; Angew. Chem. Int. Ed. 2010, 49, 6940 – 6952. [4] M. Melaimi, M. Soleilhavoup, G. Bertrand, Angew. Chem. 2010, 122, 8992 – 9032; Angew. Chem. Int. Ed. 2010, 49, 8810 – 8849. [5] D. Martin, M. Melaimi, M. Soleilhavoup, G. Bertrand, Organometallics 2011, 30, 5304 – 5313. Chem. Eur. J. 2014, 20, 1622 – 1629
www.chemeurj.org
[6] D. Enders, T. Balensiefer, Acc. Chem. Res. 2004, 37, 534 – 541. [7] D. Enders, O. Niemeier, A. Henseler, Chem. Rev. 2007, 107, 5606 – 5655. [8] N. Marion, S. Dez-Gonzlez, S. Nolan, Angew. Chem. 2007, 119, 3046 – 3058; Angew. Chem. Int. Ed. 2007, 46, 2988 – 3000. [9] J. L. Moore, T. Rovis, in Asymmetric Organocatalysis, Vol. 291 of Top. Curr. Chem. (Ed.: B. List), Springer, Berlin/Heidelberg, 2009, pp. 118 – 144. [10] T. Welton, Chem. Rev. 1999, 99, 2071 – 2084. [11] T. Welton, Coord. Chem. Rev. 2004, 248, 2459 – 2477. [12] J. P. Hallett, T. Welton, Chem. Rev. 2011, 111, 3508 – 3576. [13] E. F. Connor, G. W. Nyce, M. Myers, A. Mçck, J. L. Hedrick, J. Am. Chem. Soc. 2002, 124, 914 – 915. [14] G. W. Nyce, J. A. Lamboy, E. F. Connor, R. M. Waymouth, J. L. Hedrick, Org. Lett. 2002, 4, 3587 – 3590. [15] G. A. Grasa, R. M. Kissling, S. P. Nolan, Org. Lett. 2002, 4, 3583 – 3586. [16] G. A. Grasa, T. Gveli, R. Singh, S. P. Nolan, J. Org. Chem. 2003, 68, 2812 – 2819. [17] M. H. Dunn, M. L. Cole, J. B. Harper, RSC Adv. 2012, 2, 10160 – 10162. [18] M. Feroci, I. Chiarotto, A. Inesi, Curr. Org. Chem. 2013, 17, 204 – 219. [19] P. A. Hunt, B. Kirchner, T. Welton, Chem. Eur. J. 2006, 12, 6762 – 6775. [20] V. Kempter, B. Kirchner, J. Mol. Struct. 2010, 972, 22 – 34. [21] S. B. C. Lehmann, M. Roatsch, M. Schçppke, B. Kirchner, Phys. Chem. Chem. Phys. 2010, 12, 7473 – 7486. [22] I. Skarmoutsos, D. Dellis, R. P. Matthews, T. Welton, P. A. Hunt, J. Phys. Chem. B 2012, 116, 4921 – 4933. [23] A. J. Arduengo III, S. F. Gamper, M. Tamm, J. C. Calabrese, F. Davidson, H. A. Craig, J. Am. Chem. Soc. 1995, 117, 572 – 573. [24] J. A. Cowan, J. A. C. Clyburne, M. G. Davidson, R. L. W. Harris, J. A. K. Howard, P. Kpper, M. A. Leech, S. P. Richards, Angew. Chem. 2002, 114, 1490 – 1492; Angew. Chem. Int. Ed. 2002, 41, 1432 – 1434. [25] L. A. Leites, G. I. Magdanurov, S. S. Bukalov, R. West, Mendeleev Commun. 2008, 18, 14 – 15. [26] S. D. Sarkar, S. Grimme, A. Studer, J. Am. Chem. Soc. 2010, 132, 1190 – 1191. [27] O. Hollczki, D. Gerhard, K. Massone, L. Szarvas, B. Nmeth, T. Veszprmi, L. Nyulszi, New J. Chem. 2010, 34, 3004 – 3009. [28] O. Hollczki, P. Terleczky, D. Szieberth, G. Mourgas, D. Gudat, L. Nyulszi, J. Am. Chem. Soc. 2011, 133, 780 – 789. [29] L. Crowhurst, P. R. Mawdsley, J. M. Perez-Arlandis, P. A. Salter, T. Welton, Phys. Chem. Chem. Phys. 2003, 5, 2790 – 2794. [30] P. A. Hunt, J. Phys. Chem. B 2007, 111, 4844 – 4853. [31] S. Zahn, G. Bruns, J. Thar, B. Kirchner, Phys. Chem. Chem. Phys. 2008, 10, 6921 – 6924. [32] K. Noack, P. S. Schulz, N. Paape, J. Kiefer, P. Wasserscheid, A. Leipertz, Phys. Chem. Chem. Phys. 2010, 12, 14153 – 14161. [33] R. W. Alder, P. R. Allen, S. J. Williams, J. Chem. Soc. Chem. Commun. 1995, 1267 – 1268. [34] Y.-J. Kim, A. Streitweiser, J. Am. Chem. Soc. 2002, 124, 5757. [35] H. Chen, D. R. Justes, R. G. Cooks, Org. Lett. 2005, 7, 3949 – 3952. [36] Y. Chu, H. Deng, J.-P. Cheng, J. Org. Chem. 2007, 72, 7790. [37] O. Hollczki, Z. Kelemen, L. Nyulszi, J. Org. Chem. 2012, 77, 6014 – 6022. [38] Z. Kelemen, O. Hollczki, J. Olh, L. Nyulszi, RSC Adv. 2013, 3, 7970 – 7978. [39] H. Rodrguez, G. Gurau, J. D. Holbrey, R. D. Rogers, Chem. Commun. 2011, 47, 3222 – 3224. [40] G. Gurau, H. Rodrguez, S. P. Kelley, P. Janiczek, R. S. Kalb, R. D. Rogers, Angew. Chem. 2011, 123, 12230 – 12232; Angew. Chem. Int. Ed. 2011, 50, 12024 – 12026. [41] Z. Kelemen, O. Hollczki, J. Nagy, L. Nyulszi, Org. Biomol. Chem. 2011, 9, 5362 – 5364. [42] M. Brehm, H. Weber, A. S. Pensado, A. Stark, B. Kirchner, Phys. Chem. Chem. Phys. 2012, 14, 5030 – 5044. [43] O. Hollczki, L. Nyulszi, of Top. Curr. Chem., Springer, Berlin/Heidelberg, 2013, DOI: 10.1007/128_2012_416. [44] M. Fvre, J. Pinaud, A. Leteneur, Y. Gnanou, J. Vignolle, D. Taton, K. Miqueu, J.-M. Sotiropoulos, J. Am. Chem. Soc. 2012, 134, 6776 – 6784. [45] M. Fvre, P. Coupillaud, K. Miqueu, J.-M. Sotiropoulos, J. Vignolle, D. Taton, J. Org. Chem. 2012, 77, 10135 – 10144. [46] J. P. Hallett, C. L. Liotta, G. Ranieri, T. Welton, J. Org. Chem. 2009, 74, 1864 – 1868.
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Full Paper [47] M. Y. Lui, L. Crowhurst, J. P. Hallett, P. A. Hunt, H. Niedermeyer, T. Welton, Chem. Sci. 2011, 2, 1491 – 1496. [48] S. Tsuzuki, H. Tokuda, K. Hayamizu, M. Watanabe, J. Phys. Chem. B 2005, 109, 16474 – 16481. [49] O. Hollczki, L. Nyulszi, Org. Biomol. Chem. 2011, 9, 2634 – 2640. [50] CP2K developers group, http://www.cp2k.org/. [51] S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010, 132, 154104. [52] S. Zahn, B. Kirchner, J. Phys. Chem. A 2008, 112, 8430 – 8435. [53] A. S. Pensado, M. Brehm, J. Thar, A. P. Seitsonen, B. Kirchner, ChemPhysChem 2012, 13, 1845 – 1853. [54] S. Grimme, W. Hujo, B. Kirchner, Phys. Chem. Chem. Phys. 2012, 14, 4875 – 4883. [55] R. Ahlrichs, M. B r, M. H ser, H. Horn, C. Kçlmel, Chem. Phys. Lett. 1989, 162, 165, Current version: see http://www.turbomole.de. [56] S. Grimme, J. Comput. Chem. 2006, 27, 1787 – 1799. [57] AIMAll (Version 13.11.04), Todd A. Keith, TK Gristmill Software, Overland Park KS, USA, 2013 (http://aim.tkgristmill.com). [58] F. Weinhold, R. A. Klein, Mol. Phys. 2012, 110, 565 – 579. [59] S. Tsuzuki, H. Tokuda, M. Mikami, Phys. Chem. Chem. Phys. 2007, 9, 4780 – 4784. [60] M. Brehm, B. Kirchner, J. Chem. Inf. Model. 2011, 51, 2007 – 2023. [61] R. Tonner, G. Heydenrych, G. Frenking, Chem. Asian J. 2007, 2, 1555 – 1567.
Chem. Eur. J. 2014, 20, 1622 – 1629
www.chemeurj.org
[62] T. Cremer, C. Kolbeck, K. Lovelock, N. Paape, R. Wçlfel, P. Schulz, P. Wasserscheid, H. Weber, J. Thar, B. Kirchner, F. Maier, H.-P. Steinrck, Chem. Eur. J. 2010, 16, 9018 – 9033. [63] A. Stark, M. Brehm, M. Brssel, S. B. C. Lehmann, A. S. Pensado, M. Schçppke, B. Kirchner, Top. Curr. Chem. accepted. [64] M. Brssel, M. Brehm, T. Voigt, B. Kirchner, Phys. Chem. Chem. Phys. 2011, 13, 13617 – 13620. [65] M. Brssel, M. Brehm, A. S. Pensado, F. Malberg, M. Ramzan, A. Stark, B. Kirchner, Phys. Chem. Chem. Phys. 2012, 14, 13204 – 13215. [66] J. S. Wilkes, M. J. Zaworotko, Supramol. Chem. 1993, 1, 191 – 193. [67] H. Weber, O. Hollczki, A. S. Pensado, B. Kirchner, J. Chem. Phys. 2013, 139, 084502. [68] M. Brehm, H. Weber, A. S. Pensado, A. Stark, B. Kirchner, Z. Phys. Chem. 2013, 227, 177 – 204. [69] Y. Wang, G. A. Voth, J. Am. Chem. Soc. 2005, 127, 12192 – 12193. [70] J. N. A. Canongia Lopes, A. A. H. Pdua, J. Phys. Chem. B 2006, 110, 3330 – 3335. [71] O. Hollczki, D. S. Firaha, J. Friedrich, M. Brehm, R. Cybik, M. Wild, A. Stark, B. Kirchner, J. Phys. Chem. B 2013, 117, 5898 – 5907.
Received: August 25, 2013 Revised: November 14, 2013 Published online on December 27, 2013
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