Biphasic catalysis

Keywords Heterogeneous catalysis, biphasic catalysis, ionic liquids, task-specific ionic liquids, supported ionic liquid phases... 

Keywords. Perfluorocarbons, Catalysis, Biphase System, Oxidation, C-C-CoupUng, Phospha-nes. 

A particularly interesting type of micellar catalysis is the autocatalytic self-replication of micelles [58]. Various examples have been described, but a particularly interesting case is the biphasic self-reproduction of aqueous caprylate micelles [59]. In this system ethyl caprylate undergoes hydroxyl catalysed hydrolysis to produce the free carboxylate anion, caprylate. Caprylate micelles then fonn. As these micelles fonn, they solubilize ethylcaprylate and catalyse further production of caprylate anion and caprylate micelles. 

Transition metal catalysis in liquid/liquid biphasic systems principally requires sufficient solubility and immobilization of the catalysts in the IL phase relative to the extraction phase. Solubilization of metal ions in ILs can be separated into processes, involving the dissolution of simple metal salts (often through coordination with anions from the ionic liquid) and the dissolution of metal coordination complexes, in which the metal coordination sphere remains intact. 

Since no special ligand design is usually required to dissolve transition metal complexes in ionic liquids, the application of ionic ligands can be an extremely useful tool with which to immobilize the catalyst in the ionic medium. In applications in which the ionic catalyst layer is intensively extracted with a non-miscible solvent (i.e., under the conditions of biphasic catalysis or during product recovery by extraction) it is important to ensure that the amount of catalyst washed from the ionic liquid is extremely low. Full immobilization of the (often quite expensive) transition metal catalyst, combined with the possibility of recycling it, is usually a crucial criterion for the large-scale use of homogeneous catalysis (for more details see Section 5.3.5). 

Biphasic catalysis in a liquid-liquid system is an ideal approach through which to combine the advantages of both homogeneous and heterogeneous catalysis. The reaction mixture consists of two immiscible solvents. Only one phase contains the catalyst, allowing easy product separation by simple decantation. The catalyst phase can be recycled without any further treatment. However, the right combination of catalyst, catalyst solvent, and product is crucial for the success of biphasic catalysis [22]. The catalyst solvent has to provide excellent solubility for the catalyst complex without competing with the reaction substrate for the free coordination sites at the catalytic center. 

From all this, it becomes understandable why the use of traditional solvents (such as water or butanediol) for biphasic catalysis has only been able to fulfil this potential in a few specific examples [23], whereas this type of highly specialized liquid-liquid biphasic operation is an ideal field for the application of ionic liquids, mainly due to their exactly tunable physicochemical properties (see Chapter 3 for more details). 

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. 

In dimerization and oligomerization reactions, ionic liquids have already proven to be a highly promising solvent class for the transfer of established catalytic systems into biphasic catalysis. 

Biphasic catalysis is not a new concept for oligomerization chemistry. On the contrary, the oligomerization of ethylene was the first commercialized example of a biphasic, catalytic reaction. The process is known under the name Shell Higher Olefins Process (SHOP) , and the first patents originate from as early as the late 1%0 s. 

For this specific task, ionic liquids containing allcylaluminiums proved unsuitable, due to their strong isomerization activity [102]. Since, mechanistically, only the linkage of two 1-butene molecules can give rise to the formation of linear octenes, isomerization activity in the solvent inhibits the formation of the desired product. Therefore, slightly acidic chloroaluminate melts that would enable selective nickel catalysis without the addition of alkylaluminiums were developed [104]. It was found that an acidic chloroaluminate ionic liquid buffered with small amounts of weak organic bases provided a solvent that allowed a selective, biphasic reaction with [(H-COD)Ni(hfacac)]. 

The use of pyrrole and N-methylpyrrole was found to be preferable. Through the addition of N-methylpyrrole, all cationic side reactions could be effectively suppressed, and only dimerization products produced by Ni-catalysis were obtained. In this case the dimer selectivity was as high as 98 %. Scheme 5.2-21 shows the catalytic system that allowed the first successful application of [(H-COD)Ni(hfacac)] in the biphasic linear dimerization of 1-butene. 

In comparison with traditional biphasic catalysis using water, fluorous phases, or polar organic solvents, transition metal catalysis in ionic liquids represents a new and advanced way to combine the specific advantages of homogeneous and heterogeneous catalysis. In many applications, the use of a defined transition metal complex immobilized on a ionic liquid support has already shown its unique potential. Many more successful examples - mainly in fine chemical synthesis - can be expected in the future as our loiowledge of ionic liquids and their interactions with transition metal complexes increases. 

The major advantage of the use of two-phase catalysis is the easy separation of the catalyst and product phases. FFowever, the co-miscibility of the product and catalyst phases can be problematic. An example is given by the biphasic aqueous hydro-formylation of ethene to propanal. Firstly, the propanal formed contains water, which has to be removed by distillation. This is difficult, due to formation of azeotropic mixtures. Secondly, a significant proportion of the rhodium catalyst is extracted from the reactor with the products, which prevents its efficient recovery. Nevertheless, the reaction of ethene itself in the water-based Rh-TPPTS system is fast. It is the high solubility of water in the propanal that prevents the application of the aqueous biphasic process [5]. 

To overcome these limitations, there has been a great deal of investigation of novel methods, one of them focused on the search for alternative solvents [6, 7]. Table 5.3-1 gives different approaches to biphasic catalysis, with some of their respective advantages and limitations. 

Flowever, information concerning the characteristics of these systems under the conditions of a continuous process is still very limited. From a practical point of view, the concept of ionic liquid multiphasic catalysis can be applicable only if the resultant catalytic lifetimes and the elution losses of catalytic components into the organic or extractant layer containing products are within commercially acceptable ranges. To illustrate these points, two examples of applications mn on continuous pilot operation are described (i) biphasic dimerization of olefins catalyzed by nickel complexes in chloroaluminates, and (ii) biphasic alkylation of aromatic hydrocarbons with olefins and light olefin alkylation with isobutane, catalyzed by acidic chloroaluminates. 

As far as industrial applications are concerned, the easy scale-up of two-phase catalysis can be illustrated by the first oxo aqeous biphasic commercial unit with an initial annual capacity of 100,000 tons extrapolated by a factor of 1 24,000 (batch-wise laboratory development production reactor) after a development period of 2 years [4]. 

The fact that ionic liquids with weakly coordinating anions can combine, in a unique manner, relatively high polarity with low nucleophilicity allows biphasic catalysis with highly electrophilic, cationic Ni-complexes to be carried out for the first time [26]. 

Indeed, these reactions proceed at 25 °C in ethanol-aqueous media in the absence of transition metal catalysts. The ease with which P-H bonds in primary phosphines can be converted to P-C bonds, as shown in Schemes 9 and 10, demonstrates the importance of primary phosphines in the design and development of novel organophosphorus compounds. In particular, functionalized hydroxymethyl phosphines have become ubiquitous in the development of water-soluble transition metal/organometallic compounds for potential applications in biphasic aqueous-organic catalysis and also in transition metal based pharmaceutical development [53-62]. Extensive investigations on the coordination chemistry of hydroxymethyl phosphines have demonstrated unique stereospe-cific and kinetic propensity of this class of water-soluble phosphines [53-62]. Representative examples outlined in Fig. 4, depict bidentate and multidentate coordination modes and the unique kinetic propensity to stabilize various oxidation states of metal centers, such as Re( V), Rh(III), Pt(II) and Au(I), in aqueous media [53 - 62]. Therefore, the importance of functionalized primary phosphines in the development of multidentate water-soluble phosphines cannot be overemphasized. 

Biocatalysis localization in the biphasic medium depends on physicochemical properties of the reactants. When all the chemical species involved in the reaction are hydro-phobic, catalysis occurs at the liquid-liquid interface. However, when the substrate is hydrophobic (initially dissolved in the apolar phase) and the product is hydrophilic (remains in the aqueous phase), the reaction occurs in the aqueous phase [25]. The majority of biphasic systems use sparingly water-soluble substrates and yield hydrophobic products therefore, the aqueous phase serves as a biocatalyst container [34,35] [Fig. 2(a)]. Nevertheless, in some systems, one of the reactants (substrate or product) can be soluble in the aqueous phase [23,36-38] (Fig. 2(b), (c)). 

The use of thermomorphic systems has recently been studied as a way of achieving catalyst separation in homogeneous catalysis. For example, a biphasic hydroformylation catalyst system was developed to take advantage of the unusual solvent characteristics of perfluorocarbons combined with typical organic solvents (4). Fluorous/organic mixtures such as perfiuoromethylcyclohexane... 

Rhodium catalysis in an aqueous-organic biphasic system was highly effective for intramolecular [2+2+2] cyclotrimerization. It has been shown that the use of a biphasic system could control the concentration of an organic hydrophobic substrate in the aqueous phase, thus increasing the reaction selectivity. The intramolecular cyclization for... 

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