Ionic liquid stability

Anderson, J.L., and Armstrong, D.W., High stability ionic liquids. A new class of stationary phases for gas chromatography. Anal. Chem., 75,4851-4858,2003. 

Fujita K, Macfarlane DR, Forsyth M (2005) Protein solubilizing and stabilizing ionic liquids. Chem Commun (38) 4804-4806... 

Eor ionic liquids that do not mix completely with water (and which display sufficient hydrolysis stability), there is an easy test for acidic impurities. The ionic liquid is added to water and a pEf test of the aqueous phase is carried out. If the aqueous phase is acidic, the ionic liquid should be washed with water to the point where the washing water becomes neutral. Eor ionic liquids that mix completely with water we recommend a standardized, highly proton-sensitive test reaction to check for protic impurities. 

Water in an ionic liquid may be a problem for some applications, but not for others. However, one should in all cases know the approximate amount of water present in the ionic liquid used. Moreover, one should be aware of the fact that water in the ionic liquid may not be inert and, furthermore, that the presence of water can have significant influence on the physicochemical properties of the ionic liquid, on its stability (some wet ionic liquids may undergo hydrolysis with formation of protic impurities), and on the reactivity of catalysts dissolved in the ionic liquid. 

Without a doubt, tetrafluoroborate and hexafluorophosphate ionic liquids have shortcomings for larger-scale technical application. The relatively high cost of their anions, their insufficient stability to hydrolysis for long-term application in contact with water (formation of corrosive and toxic HF during hydrolysis ), and problems related to their disposal have to be mentioned here. New families of ionic liquid that should meet industrial requirements in a much better way are therefore being developed. FFowever, these new systems will probably be protected by state of matter patents. 

Despite the utility of chloroaluminate systems as combinations of solvent and catalysts in electrophilic reactions, subsequent research on the development of newer ionic liquid compositions focused largely on the creation of liquid salts that were water-stable [4], To this end, new ionic liquids that incorporated tetrafiuoroborate, hexafiuorophosphate, and bis (trifiuoromethyl) sulfonamide anions were introduced. While these new anions generally imparted a high degree of water-stability to the ionic liquid, the functional capacity inherent in the IL due to the chloroaluminate anion was lost. Nevertheless, it is these water-stable ionic liquids that have become the de rigueur choices as solvents for contemporary studies of reactions and processes in these media [5],... 

The following discussion concerns the thermal liquidus ranges available in different ionic liquids, as functions of cation and anion structure and composition. In particular, those structural features of cation and anion that promote these properties (while providing other desirable, and sometimes conflicting characteristics of the liquid, such as low viscosity, chemical stability, etc.) and variations in liquidus ranges and stabilities are the focus of this chapter. 

Ngo et al. [24] have shown that the thermal decomposition of ionic liquids, measured by TGA, varies depending on the sample pans used. Increased stabilization of up to 50 °C was obtained in some cases on changing from aluminium to alumina sample pans. 

Table 3.1-5 Melting points and heats of fusion for isomeric [BMIM][PFg] and [PMIM][PFs] ionic liquids, showing melting point and crystal stability increasing with the degree of branching in the alkyl substituent.

A key criterion for selection of a solvent for electrochemical studies is the electrochemical stability of the solvent [12]. This is most clearly manifested by the range of voltages over which the solvent is electrochemically inert. This useful electrochemical potential window depends on the oxidative and reductive stability of the solvent. In the case of ionic liquids, the potential window depends primarily on the resistance of the cation to reduction and the resistance of the anion to oxidation. (A notable exception to this is in the acidic chloroaluminate ionic liquids, where the reduction of the heptachloroaluminate species [Al2Cl7] is the limiting cathodic process). In addition, the presence of impurities can play an important role in limiting the potential windows of ionic liquids. 

Thermodynamic information can also be obtained from simulations. Currently we are measuring the differences in chemical potential of various small molecules in dimethylimidazolium chloride. This involves gradually transforming one molecule into another and is a computationally intensive process. One preliminary result is that the difference in chemical potential of propane and dimethyl ether is about 17.5 kj/mol. These molecules are similar in size, but differ in their polarity. Not surprisingly, the polar ether is stabilized relative to the non-polar propane in the presence of the ionic liquid. One can also investigate the local arrangement of the ions around the solute and the contribution of different parts of the interaction to the energy. Thus, while both molecules have a favorable Lennard-Jones interaction with the cation, the main electrostatic interaction is that between the chloride ion and the ether molecule. 

The author anticipates that the further development of transition metal catalysis in ionic liquids will, to a significant extent, be driven by the availability of new ionic liquids with different anion systems. In particular, cheap, halogen-free systems combining weak coordination to electrophilic metal centers and low viscosity with high stability to hydrolysis are highly desirable. 

Obviously, the use of a nonvolatile ionic liquid simplifies the distillative workup of volatile products, especially in comparison with the use of low-boiling solvents, where it may save the distillation of the solvent during product isolation. Moreover, common problems related to the formation of azeotropic mixtures of the volatile solvents and the product/by-products formed are avoided by use of a nonvolatile ionic liquid. In the Rh-catalyzed hydroformylation of 3-pentenoic acid methyl ester it was even found that the addition of ionic liquid was able to stabilize the homogeneous catalyst during the thermal stress of product distillation (Figure 5.2-1) [21]. This option may be especially attractive technically, due to the fact that the stabilizing effects could already be observed even with quite small amounts of added ionic liquid. 

Figure 5.2-1 Stabilization of the active rhodium catalyst by addition of the ionic liquid...

Catalytic oxidation reactions in ionic liquids have been investigated only very recently. This is somewhat surprising in view of the well loiown oxidation stability of ionic liquids, from electrochemical studies [11], and the great commercial importance of oxidation reactions. Moreover, for oxidation reactions with oxygen, the nonvolatile nature of the ionic liquid is of real advantage for the safety of the reaction. While the application of volatile organic solvents may be restricted by the formation of explosive mixtures in the gas phase, this problem does not arise if a nonvolatile ionic liquid is used as the solvent. 

In the author s group, much lower-melting benzenesulfonate, tosylate, or octyl-sulfate ionic liquids have recently been obtained in combination with imidazolium ions. These systems have been successfully applied as catalyst media for the biphasic, Rh-catalyzed hydroformylation of 1-octene [14]. The catalyst activities obtained with these systems were in all cases equal to or even higher than those found with the commonly used [BMIM][PF6]. Taking into account the much lower costs of the ionic medium, the better hydrolysis stability, and the wider disposal options relating to, for example, an octylsulfate ionic liquid in comparison to [BMIM][PF6], there is no real reason to center future hydroformylation research around hexafluorophosphate ionic liquids. 

The authors describe a stabilizing effect of the ionic liquid on the palladium catalyst. In almost all reactions no precipitation of elemental palladium was observed, even at complete conversion of the aromatic halide. The reaction products were isolated by distillation from the nonvolatile ionic liquid. 

Unfortunately, investigations with ionic liquids containing high amounts of AlEtCl2 showed several limitations, including the reductive effect of the alkylaluminium affecting the temperature stability of the nickel catalyst. At very high alkylaluminium concentrations, precipitation of black metallic nickel was observed even at room temperature. 

Notwithstanding their very low vapor pressure, their good thermal stability (for thermal decomposition temperatures of several ionic liquids, see [11, 12]) and their wide operating range, the key property of ionic liquids is the potential to tune their physical and chemical properties by variation of the nature of the anions and cations. An illustration of their versatility is given by their exceptional solubility characteristics, which make them good candidates for multiphasic reactions (see Section 5.3.4). Their miscibility with water, for example, depends not only on the hydrophobicity of the cation, but also on the nature of the anion and on the temperature. 

As well as phosphorus ligands, heterocyclic carbenes ligands 10 have proven to be interesting donor ligands for stabilization of transition metal complexes (especially palladium) in ionic liquids. The imidazolium cation is usually presumed to be a simple inert component of the solvent system. However, the proton on the carbon atom at position 2 in the imidazolium is acidic and this carbon atom can be depro-tonated by, for example, basic ligands of the metal complex, to form carbenes (Scheme 5.3-2). 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

Despite all the advantages of this process, one main limitation is the continuous catalyst carry-over by the products, with the need to deactivate it and to dispose of wastes. One way to optimize catalyst consumption and waste disposal was to operate the reaction in a biphasic system. The first difficulty was to choose a good solvent. N,N -Dialkylimidazolium chloroaluminate ionic liquids proved to be the best candidates. These can easily be prepared on an industrial scale, are liquid at the reaction temperature, and are very poorly miscible with the products. They play the roles both of the catalyst solvent and of the co-catalyst, and their Lewis acidities can be adjusted to obtain the best performances. The solubility of butene in these solvents is high enough to stabilize the active nickel species (Table 5.3-3), the nickel... 

A similar catalytic dimerization system has been investigated [40] in a continuous flow loop reactor in order to study the stability of the ionic liquid solution. The catalyst used is the organometallic nickel(II) complex (Hcod)Ni(hfacac) (Hcod = cyclooct-4-ene-l-yl and hfacac = l,l,l,5,5,5-hexafluoro-2,4-pentanedionato-0,0 ), and the ionic liquid is an acidic chloroaluminate based on the acidic mixture of 1-butyl-4-methylpyridinium chloride and aluminium chloride. No alkylaluminium is added, but an organic Lewis base is added to buffer the acidity of the medium. The ionic catalyst solution is introduced into the reactor loop at the beginning of the reaction and the loop is filled with the reactants (total volume 160 mL). The feed enters continuously into the loop and the products are continuously separated in a settler. The overall activity is 18,000 (TON). The selectivity to dimers is in the 98 % range and the selectivity to linear octenes is 52 %. 

As with organic solvents, proteins are not soluble in most of the ionic liquids when they are used as pure solvent. As a result, the enzyme is either applied in immobilized form, coupled to a support, or as a suspension in its native form. For production processes, the majority of enzymes are used as immobilized catalysts in order to facilitate handling and to improve their operational stability [24—26]. As support, either inorganic materials such as porous glass or different organic polymers are used [27]. These heterogeneous catalyst particles are subject to internal and external... 

In 1984, Magnuson et al. (Entry 1) investigated the influence of ethylammoni-um/water mixtures on enzyme activity and stability [29]. At low [H3NEt][N03] concentrations, an increased activity of alkaline phosphatase was found. The same ionic liquid was used by Flowers and co-workers, who found improved protein refolding after denaturation (Entry 2) [30]. 

In the first publication describing the preparative use of an enzymatic reaction in ionic liquids, Erbeldinger et al. reported the use of the protease thermolysin for the synthesis of the dipeptide Z-aspartame (Entry 6) [34]. The reaction rates were comparable to those found in conventional organic solvents such as ethyl acetate. Additionally, the enzyme stability was increased in the ionic liquid. The ionic liquid was recycled several times after the removal of non-converted substrates by extraction with water and product precipitation. Recycling of the enzyme has not been reported. It should be noted, however, that according to the log P concept described in the previous section, ethyl acetate - with a value of 0.68 - may interfere with the pro-... 

Iborra and co-workers (Entry 8) examined the transesterification of N-acetyl-i-tyrosine ethyl ester in different ionic liquids and compared their stabilizing effect relative to that found with 1-propanol as solvent [36]. Despite the fact that the enzyme activity in the ionic liquids tested reached only 10 to 50 % of the value in 1-propanol, the increased stability resulted in higher final product concentrations. Fixed water contents were used in both studies. 

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