Reaction performance, immobilized

When performing catalytic reactions or reactions with immobilized reactants, a bed or support has to be fiUed into a tube or capillary. The fiUing may be a bed of powder, a bed of granules or a three-dimensional material network (e.g. a polymerized foam). By special choice of the filling, e.g. very regularly sized particles, it is attempted to improve the flow characteristics. 

A microwave-assisted Suzuki reaction performed in a microreactor device has been discussed in Section 4.5 [153]. More examples of microwave-assisted transformations involving immobilized catalysts are described in ref. [154]. 

In the last decade there were many papers published on the study of enzyme catalyzed reactions performed in so-called chromatographic reactors. The attractive feature of such systems is that during the course of the reaction the compounds are already separated, which can drive the reaction beyond the thermodynamic equilibrium as well as remove putative inhibitors. In this chapter, an overview of such chromatographic bioreactor systems is given. Besides, some immobilization techniques to improve enzyme activity are discussed together with modern chromatographic supports with improved hydrodynamic characteristics to be used in this context. 

One of the first cross-coupling reactions performed on solid supports was the Stille reaction [250] which is a paUadium-catalyzed reaction of a trialkylaryl or trialkylalkenyl stannane with an aromatic iodide, bromide or triflate. In contrast to the process in liquid-phase, the organotin reagent is easily removed from the solid-phase because of the subsequent washing processes. Immobilized aryl halides have been frequently coupled with aryl and alkenylstannanes, whereas stan-nanes attached to the solid support have been used less frequently for the StiUe reaction. An example is the synthesis of a benzodiazepine library by EUman et al. Recently, a Stille cross-couphng reaction has been employed in the synthesis of al-kenyldiarylmethanes (ADAM) series of non-nucleoside HlV-1 Reverse Transcriptase Inhibitors (Scheme 3.14) [251]. 

The analysis of the diffusion-controlled computer simulations confirms once more conclusions drawn above for the static reactions of immobile particles. In particular, the superposition approximation gives the best lower bound estimate of the kinetics reaction, n = n(i). Divergence of computer simulations and analytical theory being negligible for equal concentrations become essential for large depths and when one of reactants is in excess. The obtained results allow us to use the superposition approximation for testing the applicability of simple equations of the linear theory in those cases when computer simulations because of some reasons cannot be performed. Examples will be presented in Chapter 6. 

Pereira et al. (17) did not observe differences on acid conversion with alcohol varying between C4 and CIO in reactions performed with C. rugosa lipase immobilized on chitosan. However, Manjon et al. (23) working with M. miehei lipase immobilized on Celite verified that esterification yields decreased as the chain length of the acid or alcohol increased, with the alcohol length having a higher influence than the acid. 

In the limonene oxidation reaction, various immobilized systems have been tested as catalyst. The use of MTO supported on poly(vinylpyridine) polymers however turned out to be a poor system for the limonene oxidation since both the conversions and the selectivities were quite a bit lower than the optimal non-immobilized system [56]. These systems were also used in combination with ionic liquids, and here, a similar result as with the non-immobilized system was found, yielding mostly diepoxide, with the best-performing catalyst MTO/PVP-25% in [BMIM][BF4], giving 92% of diepoxide at full conversion [61]. 

Reaction performance. Supercritical carbon dioxide was used as a reaction media for the enzymatic synthesis of oleyl oleate directly from oleic acid and oleyl alcohol. Reaction was catalyzed by immobilized lipase from Rhizomucor miehei-Ltpozyme IM. Reactions were carried out in the high pressure batch and continuous reactor. 

Several thermodynamic and kinetic behaviors of enzyme-catalyzed reactions performed in ILs, with respect to enzymatic reactions carried out in conventional solvents, could lead to an improvement in the process performance [34—37]. ILs showed an over-stabilization effect on biocatalysts [38] on the basis of the double role played by these neoteric solvents ILs could provide an adequate microenvironment for the catalytic action of the enzyme (mass transfer phenomena and active catalytic conformation) and if they act as a solvent, ILs may be regarded as liquid immobilization supports, since multipoint enzyme-1L interactions (hydrogen. Van der Waals, ionic, etc.) may occur, resulting in a flexible supramolecular not able to maintain the active protein conformation [39]. Their polar and non-coordinating properties hold considerable potential for enantioselective reactions since profound effects on reactivities and selectivities are expected [40]. In recent years attention has been focused on the appUcation of ILs as reaction media for enantioselective processes [41—43]. 

Poly(ethylene glycol) grafted on crosslinked polystyrene (PEG-PS) resin has often been used as a polymer support for chiral catalysts of reactions performed in aqueous media. Peptides immobilized to PEG-PS resin have been developed and used as a catalyst for direct asymmetric aldol reactions in aqueous media (Scheme 3.19) [42]. When tripeptide-supported PEG-PS 67 was used as chiral catalyst in the reaction between 70 and acetone, the corresponding aldol product 69 was obtained with 73% ee. Kudo further developed the one-pot sequential reaction of acidic deacetalization and enanhoselective aldol reaction by using an Amberhte and PEG-ST-supported peptide catalyst 67 [43]. The enantioenriched aldol product 72 was obtained in 74% isolated yield from acetal 70 in a one-pot reaction (Scheme 3.20). 

Attempts to perform the same reaction on immobilized secondary amino adds failed, giving instead N-alkylated imidazolidinones. 

Maruta, K., Teradaira, R., Watanabe, N., Nagatsu, T., Asano, M., Yamamoto, K., Matsumoto, T., Shionoya, Y., and Fujita, K. (1989). Simple sensitive assay of polyamines by high-performance liquid chromatography with electrochemical detection after post-column reaction with immobilized polyamine oxidase. Clin. Chem. 35(8), 1694-1696. 

Grether and Waldmann [15] developed an enzyme-labile safety catch linker 1 tested in intermolecular Mizoroki-Heck reactions (Scheme 14.1). This linker releases alcohols and amines through enzymatic cleavage of the benzylamide moiety followed by snbsequent lactam formation. After a Mizoroki-Heck reaction performed on an immobilized iodoarene... 

Davis and Hanson developed a new concept of immobilizing homogeneous catalysts denoted as supported aqueous phase catalysts (SAPC) [15]. They reasoned that in aqueous biphasic catalysis the reaction mainly takes place at the interface. In order to increase this interface they used a high-surface-area hydrophilic support (figure 5). These materials have a thin film of water adhered to the surface, in which the water-soluble catalyst is dissolved. The reaction, performed in an organic solvent such as toluene, occurs at the water-organic interface. The supported catalyst has a... 

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