Salting-out in Aqueous Solutions of Ionic Liquids and K3PO4: Aqueous Biphasic Systems and Salt Precipitation

The salting-out effect produced by the addition of potassium phosphate, K3PO4 to aqueous solutions of water-miscible ionic liquids, viz. 1-ethyl-3-methylimidazolium ethyl sulfate, 1-butyl-3-methylimidazolium methyl sulfate, or 1-alkyl-3-methylimidazolium chloride (alkyl = butyl, octyl or decyl) is investigated. The effects are analyzed using both the corresponding temperature–composition pseudo-binary and composition ternary phase diagrams. Different regions of liquid-liquid and solid-liquid phase demixing are mapped. The phase behavior is interpreted taking into account the complex and competing nature of the interactions between the ionic liquid, the inorganic salt and water. In the case of solutions containing 1-octyl- or 1-decyl-3-methylimidazolium chloride, the smaller magnitude of the salting-out effects is explained in terms of the possibility of self-aggregation of the ionic liquid.


Introduction
Recently, Rogers and co-workers [1,2] demonstrated that the addition of potassium phosphate, K 3 PO 4 -a water-structuring (kosmotropic) inorganic salt -to an aqueous solution of a hydrophilic ionic liquid produces a salting-out effect that leads to the formation of aqueous biphasic systems (ABS).
Besides their well-known biochemical use [3], the range of applications of ABS has recently been extended to various separation processes [4,5]. In fact ABS can be considered (just like ionic liquids often are) as novel, "green" extraction media [5]. The use of aqueous solutions of ionic liquids to promote the formation of ABS represents the meeting of two emergent areas of "green" chemistry.
The first studies on the solubility of ionic liquids in water appeared almost a decade ago [6,7]. In a recent work [8] we analyzed the effect of the addition of different inorganic salts on the phase behavior of 1-butyl-3-methylimidazolium tetrafluoroborate, [C 4 4 ], aqueous solutions, which are homogenous at room temperature but exhibit liquid-liquid demixing below 277.6 K [6, 9,10]. Whereas Roger and co-workers [1,2] investigated the phenomenon of salting-out at room temperature, we studied the temperature dependence of the demixing loci upon the addition of the inorganic salt, namely the increase of the temperature-composition heterogeneous domains in quasi-binary mixtures of (water + [C 4 4 ] + inorganic salt) as compared to those observed in the corresponding binary (water + [C 4

Results
Salting-out effects produced by the addition of K 3 PO 4 to different aqueous solutions of watermiscible ionic liquids are depicted as temperature-composition (T-w) phase diagrams in Figure 1 (sulfate-based ionic liquids) and Figure 2 (chloride-based ionic liquids). The liquid-liquid (L-L) and liquid-solid (L-S) equilibrium lines were constructed via the determination of the corresponding cloudpoint temperatures. Several fixed concentrations of K 3 PO 4 in water were considered. Data are also given in Table 1 (sulfate-based ionic liquids) and Table 2 (chloride based ionic liquids). It must be stressed that for practical reasons the ternary solutions were not prepared by addition of the inorganic salt to the ionic liquid aqueous solutions (addition of a solid to a liquid) but instead by adding the pure ionic liquid to pre-prepared K 3 PO 4 aqueous solutions (liquid to liquid addition). The main feature of the ( Figure 1a, is the precipitation of the inorganic salt from the homogeneous solution and the absence (except in one case) of ABS formation. For the three solutions with lower inorganic salt concentration (cf. Table 1) one passes directly from a homogeneous solution (when the amount of ionic liquid is low) to a twophase system (when the ionic liquid concentrations are higher) constituted by precipitated K 3 PO 4 and an aqueous ionic liquid solution. For the solution with 22.7 wt % of K 3 PO 4 , the addition of ionic liquid leads to the formation of an ABS (two-phase region), but further addition of ionic liquid results in inorganic salt precipitation (three-phase region). containing system is, in fact, striking, mainly if one points out the similarity of the two ionic liquids: overall, they differ structurally by just one methylene, -CH 2 -, group, with the alkyl side chains being more evenly distributed between the anion and cation in the former system and less so in the latter.

ABS and precipitation
The phenomenon of inorganic salt precipitation associated with ABS formation was previously reported [8] in studies involving the hydrophilic ionic liquid [C 4 mim] [BF 4 ] and the inorganic salts Na 2 SO 4 and Na 3 PO 3 . That fact did not affect the interpretation of salting out effects from the point of view of ABS formation and so it was not further examined in that work. In the current study, inorganic salt precipitation is present in the (K 3 [1] in the ABS region (I); (b) depiction of the three-phase (II) and solid-liquid (III) regions where K 3 PO 4 precipitation occurs. The arrow in (b) marks the solubility limit of K 3 PO 4 in water; the empty circles indicate experimental points where precipitation from ABS occurred. Concentrations are in weight fraction. The shaded area represents the homogeneous one-phase region.
Note that the fair symmetry of the diagram indicates that the "salting-out effect" corresponds to a mutual exclusion of the two salts, the inorganic salt and the ionic liquid, i.e, they compete for being solvated by water molecules. Ionic liquids with non-bulky ions significantly "inherited" a good portion of what makes common inorganic salts different from other compounds: the Coulomb interactions [11][12][13].
As stated in the introduction, the (K 3 PO 4 + [C 4 mim]Cl + H 2 O) system was previously studied by Rogers and coworkers [1]. Their study included the speciation of the species present in each phase of the ABS at 298 K, which allowed us to build the triangular ternary diagram presented in Figure 3a, and to compare their data with our results for the same system at that temperature. When adding the ionic liquid to the two K 3 PO 4 aqueous solutions studied in this work (cf. Figure 3a starting at the arrows and moving down the dashed lines) one crosses the boundary into the ABS region (I) delimited by the green line. Our data (red circles) are in agreement with the results reported in Ref. [1].
In order to include the precipitation of K 3 PO 4 one has to redraw diagram 3a as diagram 3b. The three-phase region (II) bounded by the orange triangle simply acknowledges two facts: i) Although K 3 PO 4 is extremely soluble in water there is a solubility limit -one cannot move down indefinitely on the left side of triangles 3a or 3b without reaching a point where water becomes saturated in K 3 PO 4 and the salt starts to precipitate. The arrow in Figure 3b indicates the approximate position of the solubility limit at 298 K [14]. The point identified by the arrow and the one corresponding to solid K 3 PO 4 define two of the orange triangle's tips. ii) When more ionic liquid is added to the ABS (moving further down the dashed line) eventually one starts to see the precipitation of K 3 PO 4 . This means that one has entered a three-phase region and (according to Gibbs rule) the compositions of each phase (for a given pressure and temperature) become fixed. The three phases in presence (liquidliquid-solid equilibrium, LLS) are a saturated K 3 PO 4 aqueous solution, solid K 3 PO 4 and an ionicliquid-rich aqueous solution. The composition of the latter defines the third tip of the triangle.
If more ionic liquid is added to the system then the amount of K 3 PO 4 -rich aqueous solution starts to diminish until it disappears. This means that the system exhibits again only two phases (liquid-solid equilibrium, LS): precipitated K 3 PO 4 and an ionic-liquid-rich aqueous solution (region III).
The fluid phase behavior of the other studied (inorganic salt + ionic liquid + water) systems can now be discussed in terms of the relative positions of regions I (ABS), II (LLS) and III (LS). In the case of the sulfate-based ionic liquids the corresponding diagrams are depicted in Figure 4 (a and b).  Figures 1b and 4b) to a system showing K 3 PO 4 precipitation only for ionic liquid weight fractions near 80 % (the [C 4 mim]Cl-based system depicted in Figures 2a and 3b), and, finally, to a system where precipitation is the most conspicuous feature (the [C 4 mim][MeOSO 3 ]-based system depicted in Figures 1a and 4a).
The shift in the position of the right tip of the three-phase region can be analyzed in terms of the relative kosmotropic nature of the different salts involved in the three ternary systems. Potassium phosphate is one of the strongest kosmotropic salts available (producing intense salting-out effects) but when it comes to aqueous solutions of hydrophilic ionic liquids there is an issue: the ionic liquid will not precipitate (as a pure solid or otherwise) which means that what can be expected at most is the separation into two aqueous solutions (the ABS) with variable amounts of water being distributed between the K 3 PO 4 -rich and ionic-liquid-rich phases. This competition for water between the two salts (K 3 PO 4 and the ionic liquid) is influenced by the ability of each salt to make strong bonds with the water molecules and/or enhance its structure, i.e. their kosmotropicity. If the ionic liquid binds strongly to water, the IL-rich phase in the ABS can have a relatively large amount of water, which means that the K 3 PO 4 -rich phase can become saturated in K 3 PO 4 (depleted in water) and precipitation can occur.
In   [16]. The formation of micelle aggregates promotes the solubility of the ionic liquids in water and thus interferes with the processes leading to ABS formation and the corresponding transition temperatures.

ABS and Micelle formation
In Figure 5 one observes that the homogeneous region increases in size (specially for ionic-liquidrich aqueous solutions at the lower right edge of the triangle diagrams) as the alkyl side-chain of the [C n mim] + cation gets longer. In this case, ABS formation is more difficult simply because the ionic liquid is more soluble in water. The kosmotropic effect of K 3 PO 4 remains intact (water is less available to form bonds with the ionic liquid due its presence) but it does not lead so readily to ABS formation because the ionic liquid can self-aggregate into micelles. Even when there is ABS formation the ionic-liquid rich phase (or micelle-rich phase) will retain a relatively small amount of water which means that the saturation of the K 3 PO 4 -rich solution is much more difficult and K 3 PO 4 precipitation is not easy to obtain -it was never observed for the systems containing [C 8 mim]Cl or [C 10 mim]Cl.

Conclusions
The results presented in this work show that salting out effects produced by the addition of a kosmotropic inorganic salt to aqueous solutions of water-soluble ionic liquids can produce ABS formation but can also lead to the precipitation of the inorganic salt. Ionic liquids that form micelles in aqueous solution can also alter significantly the pattern of ABS formation, particularly in the ionicliquid-rich regions of the corresponding ternary diagrams.
The diverse types of phase behavior observed for ternary systems based on different ionic liquids is explained phenomenologically by the analysis of the corresponding triangular ternary diagrams. From a molecular point of view, salting-out effects can be understood as a delicate balance between the interactions between the two solutes (K 3 PO 4 and the ionic liquid) and the solvent (water). Hydration theories (including the concept of kosmotropy) can explain in a semi-quantitative way the magnitude of the effects but the inbuilt complexity of aqueous solutions and ionic liquids make difficult the interpretation of such dramatic effects as those evidenced by the extensive precipitation of K 3 PO 4 in the reported [C 4 mim][MeOSO 3 ]-based system.

Experimental procedure
The onsets of phase demixing at a nominal pressure of 0.1 MPa were determined using a dynamic method with visual detection of the solution turbidity (cloud-point). For this purpose, top-narrownecked Pyrex-glass vials equipped with a magnetic stirrer were used. After being encapsulated, the solutions were frozen under vacuum and the vials sealed at the narrow neck of the open end. On warming and melting, the mixture inside the vial always occupied almost its entire internal volume (± 0.5 cm 3 ) leaving only a small dead-volume of vapor phase. The vials were placed in a glass thermostat beaker of 2 L filled with ethanol (from 253 K-293 K), water (from 293 K-333 K), or silicon oil (up to 400 K) as the thermostatic fluid. Providing continuous stirring, the solutions were cooled off or heated usually in two or three runs with the last run being carried out very slowly (the rate of temperature change near the cloud point was not greater than 5 Kh -1 ). Starting in the heterogeneous region, upon heating, the temperature at which the last sign of the turbidity disappeared was taken as the temperature of the phase transition. On the other hand, beginning in the homogeneous region, upon cooling, the temperature at which the first sign of turbidity appeared was taken as the temperature of the phase transition. Temperature (± 0.1 K) was monitored using a four-wire platinum resistance thermometer coupled to a Keithley 199 System DMM/Scanner.