Use of Ionic Liquids

Ionic liquids (IL) are also gaining acceptance as alternatives to traditional organic solvents. 

Ionic liquids are salts that are hquid at low temperatures. Unlike traditional solvents that can be described as molecular hquids, ionic hquids are composed of ions. This creates the potential to behave quite differently from conventional solvents. Due to the unique chemical physical properties of ionic hquids, they have been called green solvents . 

Especially room temperature ionic hquids (RTILs), such as those based on N,N-dialkylimidazolium ions, are interesting solvents for catal5dic reactions, for example  

Ionic liquids are non-volatile and non-flammable, eliminating the hazards associated with volatile organic compounds (VOCs). In addition, the properties of ionic liquids may be tuned by varying die identities of the cations and anions, thereby tailoring the solvent to a specific application. 

The ionic liquids show excellent extraction capabilities and allow catalysts to be used in a biphasic system for convenient recycling. For example, the hydrovinylation of styrene with ethene can be carried out successfully using an ionic liquid and supercritical CO2 as solvent (Eq. 10-15). The ionic liquid dissolves the metal organic complex catalyst and SC-CO2 facilitates mass transfer and continuous processing. 

The manufacture of ionic liquids on an industrial scale is also to be considered. [BMIMjCl is already a commercial ionic liquid that has been produced by BASF on a ton scale [47]. Chloroaluminate laboratory preparations proved to be easily extrapolated to large scale. These chloroaluminate salts are corrosive liquids in the presence of protons. When exposed to moisture, they produce hydrochloric acid, similarly to aluminum chloride. However, this can be avoided by the addition of some proton scavenger such as alkylaluminum derivatives. In Difasol technology. 

Recently, the carboxylation of epoxides was carried out in ionic liquids (ILs) that demonstrate interesting characteristics such as thermal and chemical stability, selective solubility towards organic and inorganic materials, and a high reusability of the catalysts. Taken together, these parameters make ILs useful for this type of application [151-156]. 

It is worth mentioning here that C02 is easily dissolved into the IL phase, which in turn makes the reactions of C02 possible, and also suitable. In fact, ILs have been reported as one of most efficient media for C02 fixation in the production of CCs from epoxides [157-162]. In such a case, the catalytic activity may be affected by the presence of water or air. Recently, Sun et al. [163] showed that when hydroxyl groups were added to traditional ILs, both the efficiency of the catalyst and the CC yield were increased. 

1) An easy opening of the epoxide ring, as water (acidic site) and the bromine anion of the Lewis base (basic site) coordinate different parts of the epoxide. 

2) The formation of an alkylcarbonate anion due to an interaction between the oxygen anion and C02. 

Supercritical C02 (scC02) is considered to be an economically viable and ecologically benign reaction medium for organic reactions. It has several advantages, such as no flammability, a lack of toxicity, an absence of any gas-liquid phase boundary, and possible simplifications during work-up. Kawanami et al. have reported that the fixation of C02 under supercritical conditions effectively proceeds to give CCs (Equation 7.14) [165]. 

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Chapters 1 and 2 have been reorganised and updated in line with recent developments. A new chapter on the Future of Purification has been added. It outlines developments in syntheses on solid supports, combinatorial chemistry as well as the use of ionic liquids for chemical reactions and reactions in fluorous media. These technologies are becoming increasingly useful and popular so much so that many future commercially available substances will most probably be prepared using these procedures. Consequently, a knowledge of their basic principles will be helpful in many purification methods of the future. 

The commercial availability of ionic liquids is thus a key factor for the actual success of ionic liquid methodology. Apart from the matter of lowering the activation barrier for those synthetic chemists interested in entering the field, it allows access to ionic liquids for those communities that do not traditionally focus on synthetic work. Physical chemists, engineers, electrochemists, and scientists interested in developing new analytical tools are among those who have already developed many new exciting applications by use of ionic liquids [11]. 

J. H. Davis, Jr., Working Salts Syntheses and Uses of Ionic Liquids Containing Functionalised Ions,"... 

The early history of ionic liquid research was dominated by their application as electrochemical solvents. One of the first recognized uses of ionic liquids was as a solvent system for the room-temperature electrodeposition of aluminium [1]. In addition, much of the initial development of ionic liquids was focused on their use as electrolytes for battery and capacitor applications. Electrochemical studies in the ionic liquids have until recently been dominated by work in the room-temperature haloaluminate molten salts. This work has been extensively reviewed [2-9]. Development of non-haloaluminate ionic liquids over the past ten years has resulted in an explosion of research in these systems. However, recent reviews have provided only a cursory look at the application of these new ionic liquids as electrochemical solvents [10, 11]. 

In this context, the use of ionic liquids with halogen-free anions may become more and more popular. In 1998, Andersen et al. published a paper describing the use of some phosphonium tosylates (all with melting points >70 °C) in the rhodium-catalyzed hydroformylation of 1-hexene [13]. More recently, in our laboratories, we found that ionic liquids with halogen-free anions and with much lower melting points could be synthesized and used as solvents in transition metal catalysis. [BMIM][n-CgHi7S04] (mp = 35 °C), for example, could be used as catalyst solvent in the rhodium-catalyzed hydroformylation of 1-octene [14]. 

Because of the great importance of liquid-liquid biphasic catalysis for ionic liquids, all of Section 5.3 is dedicated to specific aspects relating to this mode of reaction, with special emphasis on practical, technical, and engineering needs. Finally, Section 5.4 summarizes a very interesting recent development for biphasic catalysis with ionic liquids, in the form of the use of ionic liquid/compressed CO2 biphasic mixtures in transition metal catalysis. 

The use of ionic liquids as reaction media for the palladium-catalyzed Heck reaction was first described by Kaufmann et ak, in 1996 [85]. Treatment of bromoben-zene with butyl acrylate to provide butyl trans-cinnamate succeeded in high yield in molten tetraallcylammonium and tetraallcylphosphonium bromide salts, without addition of phosphine ligands (Scheme 5.2-16). 

One of the key factors controlling the reaction rate in multiphasic processes (for reactions talcing place in the bulk catalyst phase) is the reactant solubility in the catalyst phase. Thanks to their tunable solubility characteristics, the use of ionic liquids as catalyst solvents can be a solution to the extension of aqueous two-phase catalysis to organic substrates presenting a lack of solubility in water, and also to moisture-sensitive reactants and catalysts. With the different examples presented below, we show how ionic liquids can have advantageous effects on reaction rate and on the selectivity of homogeneous catalyzed reactions. 

Different Technical Solutions to Catalyst Separation through the Use of Ionic Liquids... 

Table 5.3-2 Different technologies for multiphasic reactions making use of ionic liquids.

To be applied industrially, performances must be superior to those of existing catalytic systems (activity, regioselectivity, and recyclability). The use of ionic liquid biphasic technology for nickel-catalyzed olefin dimerization proved to be successful. 

Although a great deal of excitement has surrounded the use of ionic liquids as solvents for organic synthesis, the rational synthesis of inorganic and organometallic compounds in ionic liquids has remained largely unexplored. 

The first use of ionic liquids in free radical addition polymerization was as an extension to the doping of polymers with simple electrolytes for the preparation of ion-conducting polymers. Several groups have prepared polymers suitable for doping with ambient-temperature ionic liquids, with the aim of producing polymer electrolytes of high ionic conductance. Many of the prepared polymers are related to the ionic liquids employed for example, poly(l-butyl-4-vinylpyridinium bromide) and poly(l-ethyl-3-vinylimidazolium bis(trifluoromethanesulfonyl)imide [38 1]. 

Thanks to their special properties and potential advantages, ionic liquids may be interesting solvents for biocatalytic reactions to solve some of the problems discussed above. After initial trials more than 15 years ago, in which ethylammonium nitrate was used in salt/water mixtures [29], results from the use of ionic liquids as pure solvent, as co-solvent, or for biphasic systems have recently been reported. The reaction systems are summarized in Tables 8.3-1 and 8.3-2, below. Table 8.3-1 compiles all biocatalytic systems except lipases, which are shown separately in 8.3-2. Some of the entries are discussed in more detail below. 

So far only two groups have reported details of the use of ionic liquids with wholecell systems (Entries 3 and 4) [31, 32]. In both cases, [BMIM][PF(3] was used in a two-phase system as substrate reservoir and/or for in situ removal of the product formed, thereby increasing the catalyst productivity. Scheme 8.3-1 shows the reduction of ketones with bakers yeast in the [BMIM][PF(3]/water system. 

Harrison et c /.146,147 have used PLP (Section 4.5.2) to examine the kinetics of MMA polymerization in the ionic liquid 18 (bmimPFfi). They report a large (ca 2-fold) enhancement in Ay and a reduction in At. This property makes them interesting solvents for use in living radical polymerization (Chapter 9). Ionic liquids have been shown to be compatible with ATRP14 "1 and RAFT.I57,15S However, there are mixed reports on compatibility with NMP.1 Widespread use of ionic liquids in the context of polymerization is limited by the poor solubility of some polymers (including polystyrene) in ionic liquids. 

The aspects of medium engineering summarized so far were a hot topic in biocatalysis research during the 1980s and 1990s [5]. Nowadays, all of them constitute a well-established methodology that is successfully employed by chemists in synthetic applications, both in academia and industry. In turn, the main research interests of medium engineering have moved toward the use of ionic liquids as reaction media and the employment of additives. 

To carry out the enzymatic amidation of carboxylic acids, normally two strategies are considered the use of ionic liquids or the removal of water from the reaction media at high temperature or reduced pressure. For instance, one of the first examples of the use of ionic liquids in biocatalysis has been the preparation of octanamide from octanoic acid as starting material and ammonia in the presence of CALB (Scheme 7.3) [11]. 

Scheme 5.16. In some instances, e.g. the aza-Diels-Alder reaction illustrated, Lewis acid catalysts are additionally required but use of ionic liquids greatly enhanees their ease of recovery and recycle.

The use of ionic liquids (ILs) to replace organic or aqueous solvents in biocatalysis processes has recently gained much attention and great progress has been accomplished in this area lipase-catalyzed reactions in an IL solvent system have now been established and several examples of biotransformation in this novel reaction medium have also been reported. Recent developments in the application of ILs as solvents in enzymatic reactions are reviewed. 

Recently, the use of ionic liquids instead of organic solvents has been published for the biphasic system. For PaHNL and SbHNL, the reaction rates are increased in comparison to organic solvents without a change of enantioselectivity. ... 

Thiolates, generated in situ by the action of ammonium tetra-thiomolybdate on alkyl halides, thiocyanates, and disulfides, undergo conjugate addition to a, (1-unsaturatcd esters, nitriles, and ketones in water under neutral conditions (Eq. 10. II).29 Conjugate addition of thiols was also carried out in a hydrophobic ionic liquid [bmim]PF6/water-solvent system (2 1) in the absence of any acid catalyst to afford the corresponding Michael adducts in high to quantitative yields with excellent 1,4-selectivity under mild and neutral conditions (Eq. 10.12). The use of ionic liquids helps to avoid the use of either acid or base catalysts... 

Kramer, J., Redel, E., Thomann, R. and Janiak, C. (2008) Use of ionic liquids for the synthesis of iron, ruthenium, and osmium nanopartides from their metal carbonyl precursors. Organometallics,... 

Some other studies showed that the combination of the three polymorphs with reduced crystallite size and high surface area can lead to the best photocatalysts for 4-chlorophenol degradation [37], or that particles in the dimension range 25-40 nm give the best performances [38]. Therefore, many elements contribute to the final photocatalytic activity and sometimes the increased contribution of one parameter can compensate for the decrease of another one. For example, better photocatalytic activity can be obtained even if the surface area decreases, with a concomitant increase in the crystallinity of the sample, which finally results in a higher number of electron-hole pairs formed on the surface by UV illumination and in their increased lifetime (slower recombination) [39]. Better crystallinity can be obtained with the use of ionic liquids during the synthesis [39], with a consequent increase of activity. 

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