Peculiar Concentration Dependence of H / D Exchange Reaction in 1-Butyl-3-methylimidazolium Tetrafluoroborate-D 2 O Mixtures

We have investigated the H/D exchange reaction between heavy water and an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]), throughout the whole concentration region as a function of D2O mol% at room temperature. We expected that the extent of the H/D reaction would increase linearly with increasing content of D2O, but the results show an extended N-shaped behavior having a small maximum at around 40 mol% and the reaction becomes very slow at a specific concentration around 80 mol%. We found that this non-linear concentration dependence correlates with the pD dependence of the solutions.


Introduction
Room temperature Ionic liquids (RTILs) shows versatility of their properties by interchanging cations and anions [1,2].Typical ionic liquids are composed of a large bulky, asymmetric organic cation containing nitrogen (e.g.imidazole, pyrrole, piperidine and pyridine) and a wide variety of anions ranging from simple halides to more complex organic species.The liquid structure of ionic liquids results from a balance between geometric factors and long-range electrostatic forces is a key to prevent crystallization.
When mixing water into RTILs, the following unique features were so far reported to occur in the RTILs-water mixtures.Firstly, a nearly-free hydrogen bonded band (NFHB) of water molecules which are not associated into the hydrogen-bonded water network structure is observed up to the water-rich region (～80 mol% H 2 O) in the Raman spectra of 1-butyl-3-methylimidazolium tetrafluoroborate, [bmim][BF 4 ]-water mixtures [3,4].The NFHB waters are probably very weakly interacting via H-bonding with the BF 4 anions.In previous studies, we found that the NFHB is preserved even at 77 K and the NFHB water survives, not forming the hydrogen bond network among themselves as in pure H 2 O liquid, when making the glassy water-ionic liquid solutions [5,6].
More surprisingly, even at water-rich conditions, H 2 O ice crystals and the solitary water co-exist in the solutions.These facts imply that the nearly-free hydrogen bonded state of water molecule is fairly stable once formed in the RTIL.
The final one is that the H/D exchange reaction in which HDO is generated by the rapid exchange of D between D 2 O and the C-H at position 2 of the 1-butyl-3-methylimidazolium (denoted as [bmim]) ring occurs [12,13].Now a protein H/D exchange method in deuterium solvents using NMR spectroscopy can provide the direct information on the detailed structure, dynamics, folding and local fluctuations [14,15].Actually, whether the hydrogens are buried or at the solvent-exposed surface is quantitatively predictable from the exchange rates for hydrogens [16].By applying this useful method to the RTIL-D 2 O mixture, the H/D exchange reaction rate in hydrophilic 1-butyl-3-methylimidazolium chloride ([bmim][Cl]) at 50˚C has been studied in detail by Nakahara et al. [13].They found a slowdown of H/D exchange reaction rate in the water-poor conditions at D 2 O below 7 M (～30 mol% D 2 O), reflecting that solitary water as a single molecule without self-associated state is deactivated in the region where the solitary water is bound strongly by the solvent ions (Cl -) as the waterwater contact is negligible compared to water in waterrich conditions.Thus the results can be understood in terms of change in the solvation dynamics in the system depending on the water concentration.
As stated above, the properties of RTILs vary depending on the combination of the cation and the anion.Importantly, the solubilities of water in RTILs highly depend on the nature of the anion.If we use the RTIL containing hydrophilic anion, the contamination of water from the atmosphere might be inevitable more or less [4].Therefore, a detailed understanding of the behavior of RTILs-water mixtures is important, e.g., for the application uses of these substances.We point out that there is a limitation of the solubility of [bmim][Cl] in water (about 48 mol% at room temperature), but [bmim][BF 4 ] is soluble in water at any concentration.In this situation, the H/D exchange reaction between heavy water and [bmim] [BF 4 ] is intriguing.We expect that the deuterated water effect might be different and this is the motivation for the current work.We have investigated the NMR spectral changes as a function of water concentration in [bmim] [BF 4 ]-D 2 O mixtures at room temperature.Here we show a peculiar concentration dependence of the H/D exchange reaction in the mixed solution.
As NMR is highly sensitive to the inter-and intra-molecular interactions, it can be used as a probe for the present purpose.The peaks of TMS (0 ppm) and TFA (0 ppm) were used as the external chemical shift standards of 1 H and 19 F NMR spectra, respectively.But when we use the double tubes, the magnetic susceptibility corrections are necessary to determine the accurate chemical shift.Thus, we used a single tube for the chemical shift measurements.5 or 100 L of 0.2 M 3-trimethylsilyl-propane sulfonic acid sodium salt (DSS) was added to the each 1 mL samples, and the peak of the DSS (0 ppm) was used as the internal chemical shift standard of the 1 H NMR spectra.
To detect the H/D exchange reaction, 1 H NMR spectroscopy was used to monitor the deuteration ratio (isotope exchange) in the [bmim][BF 4 ]-D 2 O mixtures.A hydrolysis of the BF 4 -ion in water is sometimes known to occur [17,18].We checked an extent of the hydrolysis by the 19 F NMR spectra and the pD.The pDs of each mixed solutions after the equilibration conditions were determined with a pH meter, model F-51 from Horiba co.ltd.Values of pD were obtained by adding 0.40 to the reading of the pH meter [19].We followed the H/D reaction up to 42 days and found that the time require for reaching the apparent equilibrium state is at most 1 month.At the equilibrium state, we expected that the extent of the H/D reaction would increase linearly with increasing content of D 2 O.However, the change in the I HDO / (I C(2)-H + I HDO ) with x shows an extended N-shaped behaviour having a small maximum at about x = 40.It is intriguing that at a specific concentration region of around 80 mol%, the H/D exchange reaction hardly proceeds even if the samples left for 42 days.Notably, we found that even if the temperature of the mixture at x = 80.0 was raised to 75˚C, the exchange reaction rate ( as shown in Figure 2) was sti ◎ ll slow.For a comparison, the value at x = 40.9 is also shown in the same figure.Then, the I HDO /(I C(2)-H + I HDO ) again increases steeply with further increase in the water concentration toward x = ～100.Thus, contrary to the case of the [bmim][Cl]-D 2 O mixtures, one can say that the slowdown of H/D exchange reaction moves to more "water-rich" conditions.On the other hand, the changes in the chemical shift of HDO with x are shown in Figure 3.The chemical shift of HDO increases from 3.0 ppm (x = 20.0) to 4.8 ppm (x = 100, i.e., pure D 2 O) with increasing water concentration.Normally, the higher-frequency shift is ascribed to the enhancement of hydrogen bonding between water molecules in the water structure [21].Here we quote that if a relatively hydrophobic co-solvent such as t-butyl alcohol (t-BuOH) is added to water, the chemical shift of water shows a maximum value at about 92 -94 mol% water in the water-rich region, which is envisaged by the hydrophobic hydration concept [22,23] in which t-BuOH molecules form hydrogen bonded clusters and the enhancement of water-water hydrogen bonding is promoted by the dissolved t-BuOH [24].In contrast, all of the proton signals due from the [bmim] cation (①～ ) on the ⑧ deuterium exchange showed hardly any variation in the chemical shifts up to ca. x = 90, though there were clear even small downfield shifts above x = 90.Additionally, the values of all of the signals for the mixed solutions remained unchanged with time decay from the sample preparation.The results imply that there is no indication of the specific cluster formation in the [bmim][BF 4 ]-D 2 O mixtures, such as that proposed for the t-BuOH-water mixtures.Therefore, the peculiar concentration dependence of H/D exchange reaction together with the time evolution is not originated from the structural change relating to the chemical shifts.

Results and Discussion
Next, we presumed that the rate of H/D exchange reaction might be affected by the solution pD.Then, in order to see more about the peculiar concentration dependence of H/D exchange, we performed pD measurements.The results of pD are displayed in  To understand the pDs in [bmim][BF 4 ]-D 2 O mixtures, the following information is instructive.There have been indications [25][26][27] that hydrolysis of BF 4 anion in RTILs sometimes occurs to form HF etc., though to our best knowledge there seems to have been no full-detailed study covering whole range of water concentration.The 19 F NMR spectra of the RTIL-rich phase measured by us do not show any peaks corresponding to decomposition products of the anion, pointing to the absence of signifi- cant hydrolysis in this phase, but those of the water-rich phase after x = ～75 indicated that the decomposition of the BF 4 anion proceeds with increasing x.At apparent equilibrium conditions (i.e., after 42 days sample at room temperature), the 19 F NMR measurements indicated that about 4% of the BF 4 anions hydrolyze at x = 85 mol% in the mixed solution.
cation is relatively acidic.The problem here is how acidic.Amyes et al. [28] investigated the carbon acid pK a values of imidazolium cations in aqueous solution.The reported pK a value for the imidazolium cation is 23.8 and that for the 1,3-dimethylimidazoium cation is 23.0.These are intermediate values between the pK a s of acetone (19.3) and ethyl acetate (25.6).This acidity some-As already mentioned, the C(2)-position of [bmim] times leads to undesired side reactions for the purpose of using imidazolium ionic liquids as solvents under certain reaction conditions [29].Handy and Okello [30] reported that by replacing the H with a CH 3 group the exchange became slow, though it was detectable even in the presence of a very mild base.
Considering the aforementioned results in the literatures, we presumed that the rate of H/D exchange reaction might be affected by the solution pD.To confirm this expectation, we performed the additional experiments using the buffered solutions.The mixed solutions of x = 10, 20, 40, 80, 90 and 99 mol% were adjusted to certain pDs (= 11 -12) by NaOD.As might be expected, the rate of exchange in the presence of strong base at higher x regions was found to accelerate where the reaction of the starting materials were complete quickly after mixing, done in five minutes, as shown in Figure 5.
It is interesting to refer that this results are basically in agreement with the results on the hydrolysis of imidazole-2-ylidenes (imidazole-derived carbenes) under strongly alkaline solutions (pH = 12 -13) studied by Hollóczki, et al. [31].On the other hand, in a lower D 2 O concentration region, little effect of the base on the rate of H/D exchange reaction could be detected.This is reasonable because an extent of the H/D reaction is already almost completed.We also confirmed that there were no significant acid and/or base catalysis pD effects on the chemical shifts at given concentrations (data not shown).

Conclusions
In summary, we have demonstrated the H/D exchange reaction of D 2 O in [bmim][BF 4 ] throughout the whole concentration range (x = 0 -100) at room temperature.We found that there is no linear increase in the extent of the H/D reaction with D 2 O concentration.The results show an extended N-shaped behavior having a small maximum at around 40 mol% and the reaction does hardly occurs at a specific concentration region of ～80 mol%.This is, at least partly, ascribed to the hydrolysis of BF 4 anion in this concentration region.We should keep this in mind and be cautious of the H/D exchange reaction, e.g., for the application use of [bmim][BF 4 ] in water.Although we find the good correlation between the H/D exchange reaction and the solution pD, to give a clear-cut answer for whether the peculiar concentration dependence of H/D exchange occurred at a specific concentration solely depend on the pD or not is more difficult task.The interaction between D 2 O water and the RTIL is probably anisotropic because of the inherent heterogeneity existing in the RTILs in nano-scale order that operates at a molecular level in such systems.We suppose that it may be also connected to the existence of ]-water, water-water interactions.MD simulation and small angle x-ray scattering studies would help greatly, but this is beyond the present study.We believe that the present findings denote for the fundamental importance of the substances.

Firstly, we 1 .Figure 1 .
Figure 1.Representative 1 H NMR spectrum of [bmim] [BF 4 ]-D 2 O mixtures (x = 90 mol%) at 500 MHz obtained after a deuterium exchange for the C(2)-H proton at 23.3˚C. 1 H NMR chemical shifts δ relative to TMS internal standard are shown.The exchange for deuterium of the C(2)-H of imidazolium cation in D 2 O were determined by monitoring the decay of the C(2)-H proton (②) and the deuterium exchange results in the disappearance of the signal due to the C(2)-H proton and the appearance of that due to HDO.The inset shows a chemical structure and the numbering of the skeleton atoms for the [bmim] cation.intensityincreased along with the deuterium exchange after the mixture was made.An extent of the H/D reaction with time evolution (0 -42 days) covering a whole range of the water concentration x is shown using a relative intensity ratio (I HDO /(I C(2)-H + I HDO )) of the 1 H signals of HDO and of C(2)-H in [bmim] in Figure2.We followed the H/D reaction up to 42 days and found that the time require for reaching the apparent equilibrium state is at most 1 month.At the equilibrium state, we expected that the extent of the H/D reaction would increase linearly with increasing content of D 2 O.However, the change in the I HDO / (I C(2)-H + I HDO ) with x shows an extended N-shaped behaviour having a small maximum at about x = 40.It is intriguing that at a specific concentration region of around 80 mol%, the H/D exchange reaction hardly proceeds even if the samples left for 42 days.Notably, we found that even if the temperature of the mixture at x = 80.0 was raised to 75˚C, the exchange reaction rate ( as shown in Figure2) was sti ◎ ll slow.For a comparison, the value at x = 40.9 is also shown in the same figure.Then, the I HDO /(I C(2)-H + I HDO ) again increases steeply with further increase in the water concentration toward x = ～100.Thus, contrary to the case of the [bmim][Cl]-D 2 O mixtures, one can say that the slowdown of H/D exchange reaction moves to more "water-rich" conditions.

Figure 2 .
Figure 2. The intensity ratio of the I HDO /(I C(2)-H + I HDO ) for [bmim][BF 4 ]-D 2 O mixed solution against the D 2 O concentration x.The extent of a deuterium exchange is examined with time evolution from 0 -42 days.The symbols show the data depicted.○: 0 day, △: 14 days, □: 23 days, ▽: 29 days, •: 42 days, ◎: heated for 2 hours at 75˚C immediately after the sample preparations.

Figure 4 .Figure 3 .
Figure 3.Chemical shifts of respective protons in [bmim] cation and HDO as a function of water concentration x.The chemical shifts correspond to the deviations from the position of the reference (DSS).
x is well correlated.This correlation indicates that the H/D reaction dynamics of [bmim] in D 2 O along with the minimum at x = 80 is, at least partly, connected to the solution pD.

Figure 4 .
Figure 4. Concentration dependence for the pD of [bmim] [BF 4 ]-D 2 O mixed solutions.The values for the mixed solutions after 42 days from the sample preparation are plotted.

Figure 5 .
Figure 5.The intensity ratio (I HDO /(I C(2)-H + I HDO )) of the H/D exchange reaction in buffered solutions at a basic condition (adjusted to pD = 11 -12) against the D 2 O concentration x.For a comparison, the values for the mixed solutions without the addition of the base (open circle symbols) after 42 days left from the sample preparation are plotted in the same figure.solitarywater molecules in [bmim][BF 4 ] along with the spatial heterogeneity.Further quantitative understanding of the detailed interactions existing in the system at molecular level would require e.g., a still more precise modelling of structures of [bmim]-[BF 4 ], [bmim] -water, [BF 4 ]-water, water-water interactions.MD simulation and small angle x-ray scattering studies would help greatly, but this is beyond the present study.We believe that the present findings denote for the fundamental importance of the substances.
1H and19F NMR spectra of samples of [bmim][BF 4 ] mixed with D 2 O were measured using a JEOL ECA500 (operating at 500 and 470 MHz, respectively) at room temperature (23.3˚C).Spectra widths of 1 H and19F were 9384 and 83333 Hz respectively.The digital resolutions were 0.14 Hz for 1 H and 1.27 Hz for19F spectra.To avoid a mixing of the sample solution and the NMR lock solvent, we used double tubes for the H/D measurements.The NMR lock solvent was kept in a 4 mm diameter inner glass tube and this tube was inserted in a 5 mm diameter glass tube of the sample solution.The mixture of CDCl 3 containing 1 v/v% tetramethylsilane (TMS) and D 2 O containing about 1 v/v% trifluoroacetic acid (TFA) was used as the NMR lock solvent for 1 H and19F NMR spectral measurements, respectively.