Biphasic micellar systems

From a materials point of view an incredible development happened in the twentieth century with the preparation of porous metal oxides by the decomposition of metal salts and layered oxides [30, 31], the invention of aerogels [32], and sol-gel processing [33]. In addition, the preparation of zeolites by hydrothermal processing became important for the synthesis of very well-ordered, uniform pore structures in the micropore range. In 1990, the concept of biphasic micellar systems as a template for well-ordered mesoporous materials was successfully introduced... 

Karra-Chaabouni, M., Pulvin, S., Meziani, A. et al. (2003) Biooxidation of n-hexanol by alcohol oxidase and catalase in biphasic and micellar systems without solvent. Biotechnology and Bioengineering, 81 (1), 27-32. 

Organic solvent systems include mixtures of water and water-miscible solvents, biphasic systems of water and water-immiscible solvents, pure organic solvents, and reverse micellar systems. 

In a liquid/liquid biphasic system (Figure 9.1a), the enzyme is in the aqueous phase, whereas the hydrophobic compounds are in the organic phase. In pure organic solvent (Figure 9.1b) a solid enzyme preparation is suspended in the solvent, making it a liquid/solid biphasic system. In a micellar system, the enzyme is entrapped in a hydrated reverse micelle within a homogeneous organic solvent... 

Jacobson, G.B. Tumas, W. Johnston, K.P. Biphasic catalysis in water/carbon dioxide micellar systems. US, 6,479,708, 2002. 

An overview chapter by Hamel and Hunter presents the state of the art of research on bioseparations. Extraction processes using biphasic aqueous systems, liquid membranes, reversed-micellar systems, and membrane processes are all being actively studied. Significant advances in these topics, including predictive mathematical models, are presented in the first section. The second section includes several papers on affinity and other interaction techniques that are finding uses in protein purification. In the last section, we offer several reports that delineate advances in isolation and purification processes such as electrophoresis and chromatography. 

Section 7 reviews non-aqueous biphase processes and their variations. Sections 4.5 and 4.6 deal with micellar systems and various applications of phase transfer catalysis in relation to aqueous biphase catalysis. Interestingly, biphase techniques are also being utilized from the other side, that of heterogeneous catalysis [35]. 

The first water-soluble system specifically designed to combine both functions of a ligand and a surfactant in one molecule and applied in transition-metal-cata-lyzed conversions of highly water-insoluble substrates in micellar systems is the zwitterionic tenside trisulfoalkylated tris(2-pyridyl)phosphine, 2 (n = 0, 3, 5, 7, 9, 11) [4, 14, 72, 74]. Turnover frequencies (TOF) up to 340 h-1 were achieved in the micellar hydroformylation of 1-tetradecene to pentadecanals, according to Eq. (1), using Rh/2 catalysts at 125 °C, by fine tuning of the hydrophilic/lipophilic properties of the tenside system 2 [4, 14]. In sharp contrast, Rh/TPPTS catalysts gave only traces of pentadecanals under the same biphasic conditions. 

A further technique to overcome the mass transport limitations in biphasic catalysis is the method to work in micellar [187] or reverse micellar [188] systems, that means to enhance the surface area decisively via addition of surfactants. Ren-ken found higher reaction rates and selectivities than in non-micellar systems and could hydroformylate also olefins with a long hydrocarbon chain up to C16 (see also Section 4.5). 

Other important biphasic concepts are based on the use of room-temperature ionic liquids (cf. Section 7.3) and, more recently, supercritical C02 (cf. Section 7.4) [31]. In addition, the second phase needs not necessarily to be another solvent. An amphiphilic approach can also be based on the use of micellar systems or vesicles formed by surfactants (cf. Section 4.5). A properly functionalized ligand itself can also function as the surfactant (cf. Section 3.2.4), which can even result in the formation of very stable aggregates [32]. 

Their type of micellar system belongs to the group of biphasic water/organic systems. These systems are simple and convenient in regard to regulation of equilibrium of the reactions executed therein [66,67]. The presence of an additional micellar matrix (the third micellar phase) in a biphasic system allows one to obtain extra effects in the equilibrium state, often very significant [4,68]. 

If R > I. the opposite occurs. Micellar systems arc of the inverse type, and if there is enough surfactant to produce a microemulsion it will he the type encountered in Winsor type II diagram above the biphasic region. 

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. 

The catalytic principle of micelles as depicted in Fig. 6.2, is based on the ability to solubilize hydrophobic compounds in the miceUar interior so the micelles can act as reaction vessels on a nanometer scale, as so-called nanoreactors [14, 15]. The catalytic complex is also solubihzed in the hydrophobic part of the micellar core or even bound to it Thus, the substrate (S) and the catalyst (C) are enclosed in an appropriate environment In contrast to biphasic catalysis no transport of the organic starting material to the active catalyst species is necessary and therefore no transport limitation of the reaction wiU be observed. As a consequence, the conversion of very hydrophobic substrates in pure water is feasible and aU the advantages mentioned above, which are associated with the use of water as medium, are given. Often there is an even higher reaction rate observed in miceUar catalysis than in conventional monophasic catalytic systems because of the smaller reaction volume of the miceUar reactor and the higher reactant concentration, respectively. This enhanced reactivity of encapsulated substrates is generally described as micellar catalysis [16, 17]. Due to the similarity to enzyme catalysis, micelle and enzyme catalysis have sometimes been correlated in literature [18]. 

In conclusion it can be said, that micellar effects offer useful possibilities to tune the reactivity and separation characteristics of aqueous/organic biphasic hydroformylations. Nevertheless, the added sensitivity of the systems to small changes in process variables and the added cost of surfactants and/or specially synthetized ligands have to be justified by high added value products or on grounds of process cost savings. Whether this will happen on industrial scale (perhaps in the hydroformylation of higher olefins) remains to be seen. 

The selectivity of the trap towards hydroxyl radicals was demonstrated by several control experiments using different radicals, showing that the formation of the respective hydroxylation product, 5-hydroxy-6-0-zso-propyl-y-tocopherol (57), was caused exclusively by hydroxyl radicals, but not by hydroperoxyl, alkylperoxyl, alkoxyl, nitroxyl, or superoxide anion radicals. These radicals caused the formation of spin adducts from standard nitrone-and pyrroline-based spin traps, whereas a chemical change of spin trap 56 was only observed in the case of hydroxyl radicals. This result was independent of the use of monophasic, biphasic, or micellar reaction systems in all OH radical generating test systems, the trapping product 57 was found. For quantitation, compound 57 was extracted with petrol ether, separated by adsorption onto basic alumina and subsequently oxidized in a quantitative reaction to a-tocored, the deeply red-colored 5,6-tocopheryldione, which was subsequently determined by UV spectrophotometry (Scheme 23). 

The hydroformylation of co-alkene carboxylic acid methyl esters catalysed by a Rh/TPPTS system (Scheme 1.22) in a biphasic medium does not require additives with low molecular substrates such as methyl 4-pentenoate, whereas methyl esters of higher co-alkene carboxylic acids such as methyl 13-tetra-decenoate require the presence of surfactants as mass-transfer promoters. Surfactants, indeed, decrease the interfacial tension, forming aggregates above the critical micellar concentration that speed up the catalytic process by increasing the interfacial area. 

Figure 2. Micellar autocatalysis. The biphasic system with the autocatalytic self-reproduction of aqueous caprylate micelles. Hydrolysis of supernatant ethylcaprylate (EC) takes place first at the microscopic interphase of the biphasic system and is very slow, until the cmc is reached. Then the process becomes autocatalytic (see text).

A recent and exciting area of research is the solubilization of enzymes in nonaqueous solvents. One way solubilization is achieved is through noncovalent complexes of lipid (surfactant) and protein, to be referred to here as enzyme-lipid aggregates, or ELAs. Such complexes are reported to be highly active and stable. Moreover, the activity of ELAs can be significantly higher than free, suspended enzyme (in the absence or presence of surfactant), enzymes solubilized in aqueous-organic biphasic systems, or reverse micellar solutions, and can approach catalytic rates in... 

Keywords Biphasic catalysis. Asymmetric phase-transfer catalysis. Micellar catalysis. Vesicles, Microheterogeneous systems... 

Rhodium complexes modified with polyether phosphine oxides according to the Structure 30 were used as catalysts for the hydroformylation of 1-decene and oleyl alcohol in micellar aqueous-biphase systems [56, 57]. 

Most of the other biphasic hydrogenations use also water as polar medium [130-145], Interesting variations are the use of aqueous micellar media [146] (see also Section 4.5) and the hydrogenation in aqueous media with Rh complexes which were deposited on aluminophosphate molecular sieves [147]. Other groups employed biphasic systems with fluorous solvents [148-151] or ionic liquids [152-153],... 

The successful implementation of the biphasic oxo process as the prototype of a homogeneous aqueous catalyst system will have different consequences for hydro-formylation reactions as described in Chapter 3 (development of new ligands) and Chapter 4 (solvents, co-solvents, micellar techniques) and Section 6.1.3.2. 

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