Fluorous Liquids

Fluorous catalysts are best suited for converting apolar substrates into products of higher polarity, as the partition coefficients of the substrates and products will be higher and lower, respectively, in the fluorous phase. 

It is generally considered that the major obstacle to the commercialization of reactions employing the fluorous biphasic concept is the cost of the fluorous solvent and the cost of the ligand, which must contain very large amounts of fluorine to retain the catalyst within the fluorous phase. Cost may be reduced by a proper selection 

While the nonvolatile character of IL is a major advantage over conventional solvents, it is a limitation due to the impossibility of purifying ILs by distillation. Purification can be thus a significant challenge. 

The range of homogeneous reactions that has been transposed into ILs is probably wider than into SCCO2 or perfluorinated solvents due to the great versatility of ILs. However, most of these reactions are limited to laboratory- or bench-scale with just a few examples of pilot-scale. A relevant industrial example is the Difasol process, which can be seen as an extension of the Dimersol family of processes developed by IFP [94]  

Using the ionic liquid catalyst, the Dimersol reaction can be performed as a two-phase liquid-liquid process at atmospheric pressure at between — 15 and 5 °C. Under these conditions, alkenes are immersed with activities well in excess of that found in both solvent-free and conventional solvent systems. The products of the reaction are not soluble in the ionic liquid, and form a second less-dense phase that can be separated easily. The nickel catalyst remains selectively dissolved in the ionic liquid phase, which permits both simple extraction of pure products and efficient recycling of the liquid catalyst phase. In addition to the ease of product/catalyst separation, the key benefits obtained using the ionic liquid solvent are the increased activity of the catalyst (1250 kg of propene dimerized per 1 g of Ni catalyst), better selectivity to desirable dimers (rather than higher oligomers) and the efficient use of valuable catalysts through simple recycling of the ionic liquid. 

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According to Figure 5.2 and to chemical experience, the selection of other pairs of non-miscible organic liquids is difficult and yields mainly unusual (not to say, exotic) solvents or pairs of solvents [68] such as fluorous liquids (cf. Chapter 6). This is the reason why no other organic-organic biphasic catalytic processes have yet been commercialised. 

On the heels of work by Zhu and Horvath and Rabai, perfluorocarbon solvents and fluorous reagents have been used increasingly in organic syntheses. Ruorous compounds often partition preferentially into a fluorous phase in organic/fluorous liquid-liquid extraction, thus providing easy separation of the compounds. Tris[(2-perfluorohexyl)ethyl]tin hydride combines the favorable radical reaction chemistry of trialkyltin hydrides with the favorable separation features of fluorous compounds. 

Hence, fluorous liquid crystal self assembly is an attractive area with importance for numerous practical applications and for the general understanding of the development of complexity in self-assembled systems. It is connected to other fields of soft matter research such as compartmentation of micelles and membranes... 

Fig. 6. Alkene bromination using a fluorous liquid membrane to control diffusion rates.

Another consequence of the low polarizability of perfluorocarbons is the occurrence of large miscibility gaps in solvent systems composed of perfluorocarbons and hydrocarbons. The occurrence of a third, fluorous , liquid phase in addition to the organic and aqueous phases has been extensively exploited in the convenient and supposedly ecologically benign fluorous chemistry, which will be discussed in detail in Chapter 3. 

Scheme 3.14 Examples of radical reductions by the fluorous tin hydride reagent 33. The reagent can be removed from the reaction mixture by organic-fluorous liquid-liquid extraction [2a, 3],...

Fig. 2 The temperature-dependent fluorous-liquid/liquid biphase concept.

Following the logic of this tree, the multiphase processes on the left-hand side belong among the operations with immobilized catalysts but on liquid supports . The topics of this book are the processes with the liquid supports water, supercritical fluids, ionic liquids, organic liquids, soluble polymers, and fluorous liquids among these, only two processes (Ruhrchemie/Rhone-Poulenc and Shell SHOP) are operative industrially so far. The more important leaves of the family tree are shaded in gray. 

This double meaning of the multiphasic approach is specially visible in the case of fluorous liquids, where organic chemists are at least as interested as the catalytic community in the use of these fluids. 

It might be added that the multiphase operation offers more than the decisive separation between desired products and catalyst, although there are differences between the various multiphase hquids [9]. It cannot be emphasized enough that the use of polar multiphase Hquids also separate the byproduct heavy ends from the catalyst in the system, thus avoiding a build-up in the catalyst recycle. In other processes (and probably also if very apolar fluorous liquids are used) an additional purge is needed to remove the high boilers from the catalyst, which then requires a further (and costly) separation or purification [10],... 

Looking back, it must be stated that Manassen and Beck/Joo s ideas were developed independently of each other. Remarkably, the fundamental papers of Jo6 and Kuntz created little interest and only found a wider echo in academic research once Shell and Rtihrchemie had managed to achieve industrial scale-up of their biphase catalyses in organic/organic or in aqueous systems. In a drastic departure from the normal pattern, here basic research lagged considerably behind industrial research and application [25]. This has changed with the introduction of other liquid phases such as ionic liquids (as defined today), supercritical liquids, polymeric fluids, and fluorous liquids. 

One way to conceptualize this phenomenon is to view the ponytails as short pieces of Teflon, which does not dissolve in any common solvent. As the ponytails become longer, some physical properties of the molecule approach those of Teflon. However, just as the miscibilities of fluorous liquid phases and organic liquid phases are highly temperature dependent, so are the solubilities of fluorous solids in fluorous or non-fluorous liquid phases. Hence, much higher solubilities can be achieved at elevated temperatures. This phenomenon can be used to conduct homogeneous reactions at elevated temperatures, with catalyst or reagent recovery by solid/liquid phase separation at lower temperatures. ... 

Likewise, the series of fluorous (dichloroiodo)arenes 127-129 and alkyl iodine(III) dichlorides 130-132 (Figure 5.7) have been prepared in 71-98% yields by reactions of the corresponding fluorous iodides with chlorine [69]. These compounds are effective reagents for the chlorination of alkenes (e.g., cyclooctene) and aromatic compounds (e.g., anisole, 4-rcrt-butylphenol and acetophenone). The organic chlorinated products and fluorous iodide co-products are easily separated by organic/fluorous liquid/liquid biphasic workups. The fluorous iodides can be recovered in 90-97% yields and reoxidized with chlorine [69]. 

Unconventional solvents include supercritical CO2 (scCOiX CO2-expanded liquids, " ionic liquids, fluorous liquids, and liquid polymers. The advantages and disadvantages of each are summarized in Table I. 

The liquid support may be water, supercritical fluids, ionic liquids, organic liquids or fluorous liquids [12]. The Shell higher olefin process (SHOP) and the Oxo synthesis (hydrofomylation) are examples of important industrial processes based on biphasic catalytic systems. 

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