Membrane reactors reduction

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

The reduction of acetophenone was carried out at r.t. giving 86% yield with an ee of 97%. This is similar to the ee obtained with unbound analogues. A limited study was conducted on the retention of the catalyst by nanofiltration. It was found that the compound could be retained in the membrane reactor but no specific details were given about these measurements. 

The use of such an oxazaborolidine system in a continuously operated membrane reactor was demonstrated by Kragl et /. 58] Various oxazaborolidine catalysts were prepared with polystyrene-based soluble supports. The catalysts were tested in a deadend setup (paragraph 4.2.1) for the reduction of ketones. These experiments showed higher ee s than batch experiments in which the ketone was added in one portion. The ee s vary from 84% for the reduction of propiophenone to up to >99% for the reduction of L-tetralone. The catalyst showed only a slight deactivation under the reaction conditions. The TTON could be increased from 10 for the monomeric system to 560 for the polymer-bound catalyst. 

Kragl and Wandrey made a comparison for the asymmetric reduction of acetophenone between oxazaborolidine and alcohol dehydrogenase.[59] The oxazaborolidine catalyst was bound to a soluble polystyrene [58] and used borane as the hydrogen donor. The carbonyl reductase was combined with formate dehydrogenase to recycle the cofactor NADH which acts as the hydrogen donor. Both systems were run for a number of residence times in a continuously operated membrane reactor and were directly comparable. With the chemical system, a space-time yield of 1400 g L"1 d"1 and an ee of 94% were reached whereas for the enzymatic system the space-time yield was 88 g L 1 d"1 with an ee of >99%. The catalyst half-life times were... 

This system fulfills the four above-mentioned conditions, as the active species is a rhodium hydride which acts as efficient hydride transfer agent towards NAD+ and also NADP+. The regioselectivity of the NAD(P)+ reduction by these rhodium-hydride complexes to form almost exclusively the enzymatically active, 1,4-isomer has been explained in the case of the [Rh(III)H(terpy)2]2+ system by a complex formation with the cofactor[65]. The reduction potentials of the complexes mentioned here are less negative than - 900 mV vs SCE. The hydride transfer directly to the carbonyl compounds acting as substrates for the enzymes is always much slower than the transfer to the oxidized cofactors. Therefore, by proper selection of the concentrations of the mediator, the cofactor, the substrate, and the enzyme it is usually no problem to transfer the hydride to the cofactor selectively when the substrate is also present [66]. This is especially the case when the work is performed in the electrochemical enzyme membrane reactor. 

Rautenbach and MeUis [75] describe a process in which a UF-membrane fermentor and a subsequent NF-treatment of the UF-permeate are integrated. The retentate of the NF-step is recycled to the feed of the UF-membrane reactor (Fig. 13.8). This process has been commercialised by Wehrle-Werk AG as the Biomembrat -plus system [76] and is well suited for the treatment of effluents with recalcitrant components. The process also allows for an additional treatment process, like adsorption or chemical oxidation of the NF-retentate, before returning the NF-retentate to the feed of the UF-membrane fermentor. Usually, the efficiency of these treatment processes is increased as the NF-retentate contains higher concentrations of these components. Pilot tests with landfiU leachates [75] and wastewater from cotton textile and tannery industry have been reported [77]. An overview of chemical oxygen demand (COD) reduction and COD concentrations in the permeate are shown in... 

Figure 12-4 Membrane reactor in wJiicIi a cataJyst promotes reaction in the membrane and maintains reactants and products separate. Examples sliown are CH4 oxidation to syngas and C2H6 reduction to C2H4. Tlie membrane eliminates N2 from the syngas and produces C2H4 beyond equilibrium by removing H2 in these apphcations.

Due to the behavior of the membrane reactor as a continuously operated stirred tank reactor (CSTR) [2], it can be used effectively to suppress side-reactions, for example the noncatalyzed reduction yielding the racemate in the oxazaborolidine reaction [11]. 

In a first reactor, where benzoylformate decarboxylase (BFD) is retained, benz-aldehyde and acetaldehyde are coupled to yield (S)-hydroxy-l-phenylpropanone. This hydroxy ketone is then reduced to the corresponding diol in a second reactor by an alcohol dehydrogenase (ADH). Regeneration of the necessary cofactor is achieved by formate dehydrogenase (FDH) or by other methods. To avoid additional consumption of redox equivalents by unselective reduction of residual starting material from the first reactor, the volatile aldehydes are removed via an inline stripping module between the two membrane reactors. In this setup the diol was produced with high optical purity (ee, de > 90%) at an overall space-time yield of 32 g L d . ... 

Reaction engineering helps in characterization and application of chemical and biological catalysts. Both types of catalyst can be retained in membrane reactors, resulting in a significant reduction of the product-specific catalyst consumption. The application of membrane reactors allows the use of non-immobilized biocatalysts with high volumetric productivities. Biocatalysts can also be immobilized in the aqueous phase of an aqueous-organic two-phase system. Here the choice of the enzyme-solvent combination and the process parameters are crucial for a successful application. 

Simulations based on kinetic modelling of the reduction of acetophenone with propan-2-ol, using polymer-enlarged and the unmodified catalysts, revealed that comparable performance cannot be obtained by batch operation. Polymer enlargement allowed a continuous operation of transfer hydrogenation in a chemical membrane reactor.353... 

R)-2-Hydroxy-4-phenylbutyric acid was produced continuously in an enzyme membrane reactor by enzymatic reductive animation of the a-keto acid with d-lactate dehydrogenase coupled with formate dehydrogenase (FDH) for regeneration of NADH. Reactor performance data matched a kinetic reactor model (Schmidt, 1992). 

S. Rissom, J. Beliczey, G. Giffels, U. Kragl, and C. Wan drey, Asymmetric reduction of acetophenone in membrane reactors comparison of oxazaborolidine and alcohol dehydrogenase, Tetrahedron Asymm. 1999, 10, 923-928. 

Table 8. Preparation of chiral alcohols by enzyme-catalyzed reduction of the corresponding ketones with ADH from Lactobacillus kefir. The production of phenylethanol with formate and formate dehydrogenase (FDH) for coenzyme regeneration was carried out continuously in an enzyme-membrane-reactor...

Ozone decomposition in airplanes Selective catalytic reduction of NOx Arrays of corrugated plates Arrays of fibers Gauzes Ag Methanol -> formaldehyde Pt/Rh NO production from ammonia HCN production from methane Foams Catalytic membranes reactors... 

The main applications of biocatalytic membrane reactors in the food sector include reduction of the viscosity of juices by hydrolyzing pectins, reduction of the lactose content in milk and whey by its conversion into digestible sugar, treatment of musts... 

Although enzymes have the advantage of selectivity and efficiency, they are, as previously mentioned, sometimes not very fast. To increase the total reaction time in microspace, Muller et al. [428] constructed a circulating continuous flow enzyme membrane reactor and investigated the reduction of acetophenone to (S)-phenylethanol in the presence of the enzyme alcohol dehydrogenase (ADH)... 

In addition to this increase in conversion, other benefits can be expected when using a membrane reactor. The same yields can be achieved at lower temperatures, leading to energy savings and reduced catalyst deactivation (one of the major problems of alkane dehydrogenation), increased selectivities when temperature-promoted side reactions exist or when the permeating species arc involved in these side reactions. Moreover, the formation and separation of products in the same unit leads to a reduction in capital costs. 

Enzymatic synthesis of E-tm-leucine is another example of the use of isolated enzymes (Bommarius et al, 1995). An NADH-dependent leucine dehydrogenase was used as a catalyst for the reductive amination of the corresponding keto acid together with formate dehydrogenase (FDH) and formate as a cofactor regenerator (Fig. 19.5b Shaked and Whitesides, 1980 Wichmann et al, 1981). Furthermore, a unique membrane reactor system involving FDH and PEG-modihed-NAD for continuous NADH regeneration... 

In addition to this, that an interesting novel emulsion membrane reactor concept overcomes the difficulties of the large solvent volume otherwise required for the reduction of poorly soluble ketones [30]. 2-Octanone was reduced by a carbonyl reductase from Candida parapsilosis to (S)-2-octanol with > 99.5 % ee and total turnover number of 124 - the 9-fold value of that obtained in a classical enzyme reactor. 

In addition to the Navier-Stokes equations, the convective diffusion or mass balance equations need to be considered. Filtration is included in the simulation by preventing convection or diffusion of the retained species. The porosity of the membrane is assumed to decrease exponentially with time as a result of fouling. Wai and Fumeaux [1990] modeled the filtration of a 0.2 pm membrane with a central transverse filtrate outlet across the membrane support. They performed transient calculations to predict the flux reduction as a function of time due to fouling. Different membrane or membrane reactor designs can be evaluated by CFD with an ever decreasing amount of computational time. 

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