Production of chemical products by heterogeneous enzymatic catalysis

Abstract

The invention relates to the performance of an enzymatically catalyzed condensation reaction in a hydrodynamic loop reactor with freely mobile enzymes fixed on carrier particles and with a retaining device for the catalyst particles. The loop reactor is fed by way of a mixer with a nozzle. The mixer with the nozzle undertakes mixing of the liquid reactants immediately prior to entry into the reactor, without the catalyst being exposed to high shear forces. At the same time, the jet of the nozzle drives free circulation of the catalyst particles in the loop reactor. The loop reactor reduces catalyst stress and denaturation and enables high transformation rates compared to other reactor concepts. By using a hydrodynamic loop reactor with retention of the catalyst in the loop reactor, 3-phase systems are avoided.

Description

Production of chemical products by heterogeneous enzymatic catalysis

[0001] The invention relates to carrying out an enzymatically catalyzed condensation reaction in a hydrodynamic loop reactor with freely moving enzymes fixed to support particles and with a retention device for the catalyst particles. The loop reactor is fed via a mixer with a nozzle. The mixer with the nozzle mixes the liquid reactants immediately before they enter the reactor, without subjecting the catalyst to high shear forces. At the same time, the jet from the nozzle drives the free circulation of the catalyst particles in the loop reactor. The loop reactor reduces catalyst stress and denaturation and enables high conversion rates compared to other reactor designs. By using a hydrodynamic loop reactor with catalyst retention within the loop reactor, three-phase systems are avoided.

[0002] The synthesis of condensation products such as esters, amides, amines, and ethers, with the elimination of water as a byproduct, typically takes place at high temperatures (>200°C) and is therefore energy-intensive, promotes the formation of byproducts, and causes comparatively high CO2 emissions. Product quality is crucial for most product applications.

[0003] Conventional catalysts are used, or the autocatalytic properties of the excess acidic reactant are exploited in multi-purpose batch reactors, such as stirred reactors with or without external liquid recirculation or jet-loop reactors. The products are used for various applications, for example in household cleaning, personal care, food additives / emulsifiers, pharmaceutical excipients, technical additives, or base materials for lubricants.

[0004] Enzymatically catalyzed reactions offer an alternative synthesis route. The enzymatic synthesis of condensation products can be carried out at much lower temperatures (below 100°C), which significantly reduces the energy required for the reaction and can improve product quality. Furthermore, the low reaction temperature allows for the utilization of waste heat with zero (or even negative) economic value.

[0005] Enzymatic catalysts have been known for a long time and have been studied on a laboratory and pilot scale for many years. Most enzyme catalysts for condensation reactions known in industry and literature, such as Lipuraflex® from Novozymes, are immobilized on small support particles. Liquid enzymes also exist, but these are less stable and less efficient and therefore not currently widely used.

[0006] M. Schlüter et al., Powder Technology 151 (2005) 68-76 concerns an investigation into the influence of local effects in three-phase flows on the power consumption in jet-loop reactors.

[0007] H. Warmeling et al., Chemical Engineering Science 49(2016) 229-248 is a summary of jet loop reactors, which are suitable as a safe and versatile reactor arrangement for intensifying catalytic reactions.

[0008] EP 0 787 803 Al relates to a method for carrying out enzymatic fixed-bed reactions by contacting a substrate with an enzyme immobilized on a support and packaged in a reactor, while maintaining the optimal temperature of the enzyme, wherein the method includes carrying out the reaction under adiabatic conditions and simultaneously mixing a portion of the reaction liquid with a substrate solution and circulating the resulting mixture to the reactor through a heat exchanger, thereby keeping the interior of the reactor in a state as homogeneous as possible.

[0009] EP 2 080 806 A2 relates to a process for the heterogeneously catalyzed production of carboxylic acid derivatives, wherein a circulating reactor with a reaction vessel is used in which a heterogeneous catalyst is freely distributed in the reaction mixture and an additional gas input ensures mixing in the reaction vessel.

[0010] CN 114 657 062 A relates to a reactor and a process for biodiesel deacidification using lipase catalysis. The reactor comprises an immobilized lipase loop reactor, a storage tank for short-chain alcohol, and a recirculation pump. The immobilized lipase loop reactor is equipped with a manifold, a reaction cavity, and a mixing cavity. A guide cylinder is arranged in the reaction cavity, with the upper part of the reaction cavity sequentially connected to a condenser assembly and a vacuum unit. A pump pumps the liquid short-chain alcohol from the storage tank through a pipe into the mixing cavity, allowing for precise control of the feed rate and ensuring a stable feed rate. The problem of an unstable and uncontrollable air inflow is solved by supplying the short-chain alcohol in gaseous form.A circulation pump pumps the feed liquid in the reaction cavity to the mixing cavity, thus providing circulation power.

[0011] Immobilized enzyme catalysts are in principle very efficient catalysts for condensation reactions, but are subject to various limitations that have thus far prevented widespread commercialization. A detailed analysis by the inventors of the present invention has identified the following technical problems with the use of enzyme catalysts:

[0012] (1) Immobilized catalysts are expensive and must be reusable in multiple batches to be economically attractive. Therefore, the overall catalyst productivity [kg product / (hour x kg catalyst)] is the main cost driver and must be significantly improved for enzymatic condensation reactions to become competitive with conventional condensation reactions in terms of operating costs (OPEX).

[0013] (2) Immobilized catalysts are sensitive to shear forces and cannot be used in equipment with high shear forces such as agitators, pumps and jet mixers. The be- This indicates that they generally cannot be used as replacements for conventional catalysts in existing reactors. Therefore, attempts have been made to enclose the enzyme catalyst in a separate bed within the liquid circuit. However, this leads to additional problems:

[0014] (3) If the enzyme bed is placed in the liquid circuit, a high liquid circulation rate is required to achieve adequate reaction times and adequate overall catalyst productivity, since the reaction takes place only in the bed.

[0015] (4) The enzymes are immobilized on small support particles that compress tightly under pressure. High pressure drops can lead to catalyst damage, liquid channeling, and poor liquid distribution. Therefore, fixed beds must operate at relatively low liquid velocities, which results either in low liquid circulation rates, impractical bed diameters, or expensive multi-tube bed designs. Consequently, attempts have also been made to use a fluidized bed for enzymes.

[0016] (5) The density difference between the immobilized enzyme catalyst particles and the reaction fluid is small. At high fluid turnover rates, the catalyst tends to be carried upwards because the upward viscous drag forces on the catalyst exceed the negative buoyancy forces (settlement forces). To achieve stable fluidization with conventional fluidized bed concepts, where the catalyst particles are kept in suspension, lower fluid turnover rates or large-diameter beds would be required; that is, the same problems as described above apply. The application of an additional gas flow reinforces the upward drag force. Therefore, a conventional fluidized bed or gas lift reactor can only be used with a lower fluid turnover rate. This can negatively affect the overall productivity of the catalyst.

[0017] (6) Another problem in creating a three-phase system (gaseous-solid-liquid) is the increased complexity in modeling and predicting such a system. This increases the risks of scaling up.

[0018] (7) Another problem with the introduction of an inert gas (e.g., nitrogen) and the creation of a three-phase system (gas-solid-liquid) is that the tail of the inert gas bubble can negatively affect the dispersion of the solid phase as well as the mass transfer between the solid and liquid phases. For example, the tail of the bubble can cause additional turbulence, leading to a misdistribution of the solid phase, and the bubble can adhere to the solid phase, penetrate its pores, and even completely encapsulate it. This can negatively affect the overall productivity of the catalyst as well as the final product yield.

[0019] (8) Another problem with the introduction of an inert gas (e.g. nitrogen) and the creation of a three-phase system (gas-solid-liquid) is that the gas phase can generate additional shear forces on the catalyst. This can negatively affect the overall productivity of the catalyst.

[0020] (9) Another problem with conventional fluidized bed concepts is that they may not produce uniform and defined mixing (intensive dispersion) of the catalyst phase, meaning that the catalyst particles do not participate uniformly in the reaction. This can negatively affect the overall productivity of the catalyst.

[0021] (10) Another problem with gas-lift reactors where water separation occurs directly in the enzyme bed is that a vacuum must be applied to the enzyme bed to remove the water. The vacuum, as well as the stripping effect of the stripping gas, can cause lighter reactants already present in the enzyme bed to partially evaporate, preventing them from participating in the liquid-liquid reaction. This can negatively affect the overall productivity of the catalyst and the yield of the final product. Furthermore, the enzyme can catalytically oxidize the reactants and products, which means that regular vacuum leak tests are necessary to prevent known and unknown side reactions that could degrade product quality.

[0022] (11) Another problem with gas lift reactors of the type known from CN 114 657 062 A is that the reactants enter the fluidized bed through a distributor plate with multiple openings. Orifices have low flow coefficients, meaning they suffer irreversible energy losses and can therefore transfer only a fraction of the supplied energy to drive the internal circulation in the reactor. Furthermore, the distributor is not inserted into the riser tube, and its diameter is specified as being up to 150% of the riser tube's diameter, which means that the incoming liquid and gas partially bypass the riser tube, further reducing the internal circulation and the efficiency of the design.

[0023] (12) Another problem is the enzyme's sensitivity to high temperatures. The reaction temperature must typically be below 100°C to prevent the enzyme from denaturing. At such low temperatures, water removal is challenging yet extremely important because the enzyme also catalyzes the reverse reaction (hydrolysis), and because high concentrations of water can be detrimental to the enzyme's lifespan. Therefore, it is important to keep the water concentration low throughout the reaction, and especially towards the end (approximately less than 100 ppm).

[0024] a) However, water removal in a downstream stirred reactor by conventional flashing of the reactants into the headspace under vacuum does not achieve a high gas-liquid interface for the transition of water from the liquid to the gas phase, which can lead to slow or incomplete water removal. Insufficient water removal can negatively affect the overall productivity of the catalyst as well as the final product yield.

[0025] b) Dewatering in the same reactor system leads to conflicts of interest regarding operating temperature and operating pressure. While the temperature for the reaction should be low (e.g., below 100°C) to avoid denaturing the enzyme, and the pressure should simultaneously be sufficiently high (e.g., above 1 bar (a)) to keep both reactants in the liquid phase, the temperature The temperature for water removal should be high (e.g. above 100°C) and the pressure low (e.g. below 1 bar (a)) to achieve and maintain low water concentrations.

[0026] (13) Another problem is that, due to the low operating temperature in the enzyme bed, the reactants may be partially or completely immiscible. This means that two immiscible liquid phases must meet at the surface and in the pores of a third solid phase (immobilized enzyme catalyst) for the reaction to occur. Mixing two immiscible phases into a fine dispersion requires high shear forces, which the enzyme cannot withstand. This can negatively affect the overall productivity of the catalyst as well as the final product yield.

[0027] (14) Another problem is that the enzymes are also sensitive to hydrophilic reactants (e.g., various amines and alcohols). This means that it is important to maintain a low concentration of the second hydrophilic reactant. This means that a typical batch reaction, in which the reactants are fed at the beginning and then circulate through the enzyme bed, can accelerate the denaturation of the enzyme catalyst. This can negatively affect the overall productivity of the catalyst.

[0028] It is an object of the invention to provide an energy- and enzyme-conserving enzymatically catalyzed condensation process and a system for carrying out such a process, achieving the highest possible catalyst productivity. The problems mentioned above (1) to (14) should at least be reduced or even completely solved.

[0029] This problem is solved by the subject matter of the independent patent claims.

[0030] A first aspect of the invention relates to a system for the conversion of at least two reactants in a condensation reaction to at least one reaction product and one by-product in a liquid phase under heterogeneous enzymatic catalysis, wherein the system comprises the following elements: - a hydrodynamic loop reactor configured to accommodate an enzyme immobilized on particles, wherein the particles are freely suspended in the liquid phase; - a mixer configured to mix the reactants outside the loop reactor; wherein the mixer includes a nozzle configured to inject a liquid jet comprising the mixed reactants into the liquid phase, such that the injected liquid jet causes free circulation of the particles in the liquid phase; and - a retention device configured to retain particles in the loop reactor during discharge of a liquid phase comprising reaction product and by-product from the loop reactor.

[0031] The apparatus according to the invention serves to react at least two reactants, preferably exactly two reactants, which react with each other in a condensation reaction. In the condensation reaction, at least one reaction product is formed, preferably substantially exactly one reaction product, as well as at least one by-product, preferably substantially exactly one by-product.

[0032] Examples of reactants according to the invention are carboxylic acids and alcohols, which react in a condensation reaction to form esters (reaction product) with the elimination of water (byproduct). Other examples of reaction products are amides, amines, and ethers. Such reactions are known to those skilled in the art. The reactants required for the respective reaction are often commercially available, and the byproducts eliminated in the reactions can be, in addition to water, other low-molecular-weight compounds, e.g., short-chain alcohols or hydrogen chloride.

[0033] In preferred embodiments, the reactants are miscible with each other.

[0034] In other preferred formulations, the reactants are not miscible.

[0035] The reaction takes place in a liquid phase. If the reactants and the product are liquid in pure form under the reaction conditions, it is preferred that the reaction be carried out without the use of an additional solvent. However, if the reactants or the product are not liquid under the reaction conditions, the liquid phase preferably includes a solvent. The solvent can be a single substance or a mixture of several substances.

[0036] Depending on the type of chemical reaction, i.e., the type of reactants and the enzyme used, the liquid phase may contain further additives, in particular cofactors, buffers, salts, etc. Suitable additives are known to experts and commercially available.

[0037] Depending on the type of chemical reaction, i.e., the type of reactants and any solvent used, the liquid phase can comprise two liquid subphases. This is particularly the case if the reactants are immiscible, even in the presence of any solvent.

[0038] The reaction according to the invention takes place under heterogeneous enzymatic catalysis. In addition to the liquid phase, a solid phase is also present, which is particulate and suspended in the liquid phase. The solid phase comprises or consists essentially of particles to which at least one enzyme is immobilized.

[0039] Suitable particles (solid supports) and methods for immobilizing enzymes on such supports are known to experts. Preferably, the particles are based on polymers, e.g., PMMA or polystyrene, or inorganic materials, preferably silica. Many enzymes immobilized on particles are commercially available.

[0040] The type of enzyme used depends on the type of enzymatically catalyzed condensation reaction. For example, esterases, lipases, or amidases can be used as enzymes. Suitable enzymes are known to experts and commercially available.

[0041] The reaction according to the invention takes place in a loop reactor. Loop reactors are known to those skilled in the art. Typically, a loop reactor comprises a tubular reactor and a mass recirculation system. The reaction volume and residence time can be adjusted independently of each other by the size of the reactor tube and the proportion of the recirculated mass flow. Typically, in a loop reactor, an upward flow (upflow column) and a downward flow (downflow column) are spatially separated from each other.

[0042] The loop reactor according to the invention is hydrodynamic, meaning that the reaction medium is circulated by a jet of fluid in a liquid phase. The enzyme immobilized on the particles is suspended in the circulating liquid. Hydrodynamic loop reactors are known to those skilled in the art. The circulation gently agitates the particles, allowing the enzyme immobilized on their surface to exert its catalytic activity upon contact with reactants.

[0043] Preferably, the loop reactor according to the invention is a hydrodynamic solid suspension loop reactor.

[0044] The loop reactor according to the invention is particularly preferably equipped with a Venturi nozzle as a mixer, through which a particularly effective mixing of the reactants takes place immediately before they enter the reactor. This nozzle also has the advantage that it suspends the solid phase particularly well in the liquid phase and enables the recirculation of the suspension by means of a differential pressure between the reactor and the nozzle head.

[0045] In view of the aforementioned problems (1) to (11) of conventional reaction procedures, the invention employs a hydrodynamic solid-liquid suspension jet loop reactor with internal forced circulation, comprising a riser tube and a downtube. The catalyst particles are drawn upwards through the riser tube and downwards through the downtube together with the internal liquid circulation flow, which is driven by the momentum of the liquid jet. This design requires neither a gas for upward motion nor gravity for downward motion to fluidize the catalyst. The loop reactor according to the invention can even be used to fluidize the catalyst when the density of the liquid is higher than that of the catalyst (e.g., in the case of glycerol).

[0046] This solution (1) facilitates the reuse of the enzyme for multiple batches, (2) exerts a low shear force on the enzyme, (3-5) operates with high batch turnover rates (e.g. up to 60 1 / h), (6-8) does not require an additional third gas phase, (9) produces a uniform dispersion of the catalyst in a cocurrent flow of reactants and catalyst, (10) operates under overpressure, (11) and operates without significant energy losses.

[0047] Preferably, the system according to the invention, in particular the loop reactor according to the invention, operates with high liquid recirculation rates, wherein the inherently competing and difficult-to-reconcile tasks of (a) mixing the reactants, (b) chemical reaction, and (c) removal of the by-product(s) are spatially separated, i.e., carried out in different parts of the system. The mixing of the reactants takes place in the mixer, the chemical reaction in the loop reactor, and the removal of the by-product(s) takes place after the liquid phase containing the reaction product and by-product has been discharged from the loop reactor.

[0048] In this way, each of these tasks can be performed in an ideal plant section and under ideal process conditions, i.e., (a) a high-shear, high-pressure liquid-liquid system for mixing the reactants, (b) a low-shear, low-temperature, high-pressure liquid-solid system for the reaction, and (c) a high-shear, high-temperature, low-pressure gas-liquid system for by-product removal. This setup significantly improves the overall productivity of the catalyst and makes enzymatically catalyzed reactions, such as esterification, competitive with conventional reactions on a large scale.

[0049] The reaction conditions for the conversion according to the invention are not particularly restricted and depend in particular on the type of reactants, the type of enzyme used, the type of solvent, etc.

[0050] The reaction preferably takes place at temperatures in the range of 30°C to 100°C, more preferably in the range of 50°C to 90°C.

[0051] The reaction preferably takes place at elevated pressure, in particular at a pressure greater than 1 bar (a). It is especially preferred that the reaction pressure is chosen to be high enough, depending on the reactants used, so that the reactants are in liquid form at the reaction temperature.

[0052] In preferred embodiments, no gas is fed into the loop reactor according to the invention.

[0053] The system according to the invention comprises a mixer in which the reactants are mixed together before being fed into the loop reactor. According to the invention, the mixing of the reactants thus takes place outside the loop reactor, and the mixture obtained in this way is then fed into the loop reactor.

[0054] Preferably, the mixer is a Venturi jet mixer.

[0055] It is preferred that the reactants be mixed together without solvent if they are liquids in their pure form under the reaction conditions. However, if at least one reactant or the product is solid under the reaction conditions, the reactants can also be mixed in a liquid solvent.

[0056] The order in which the reactants are mixed with each other and with solvent is not particularly restricted. In preferred embodiments, the reactants are separated and The solvents are prepared independently as solutions in or mixtures with solvent and then combined in the mixer. Additional solvent can then be added if necessary.

[0057] The mixer generates a liquid jet which is introduced into the loop reactor. For this purpose, the liquid containing the reactants, generated in the mixer, is preferably pumped and then fed into the loop reactor via a nozzle, preferably a Venturi nozzle. The momentum of the liquid jet then causes movement of the liquid phase within the loop reactor. This movement can be, for example, laminar or turbulent flow. This flow results in the circulation of the suspended particles within the liquid phase. Since the particles typically do not clump together, free circulation occurs.

[0058] For the purposes of this disclosure, free circulation of the particles in the liquid phase refers to a state in which the particles, as a suspended solid phase, are carried in cocurrent flow with the reactants throughout the entire liquid circulation of the loop reactor generated by the nozzle. The particles are therefore not held in a fixed position (e.g., in a fixed bed, between filters, or in a separate partial volume), are not accumulated by the retention device, are not permeated by the reactants in a cross-flow, and are not fluidized by a third inert gas phase. The retention device, preferably arranged in the region of a liquid outlet of the loop reactor, prevents the particles from being discharged from the loop reactor with the discharged liquid, without restricting their circulation to a partial region of the loop reactor.Preferably, the liquid outlet and the retention device are arranged in the loop reactor such that the discharged liquid flows through the retention device essentially transversely to the liquid circulation in the loop reactor towards the liquid outlet.

[0059] In preferred embodiments, the reactants are miscible with each other and the liquid jet consists of a single liquid phase.

[0060] In other preferred embodiments, the reactants are immiscible, possibly even in the presence of solvent, and the liquid jet comprises two liquid subphases. Preferably, an emulsion is then generated by the mixer and this emulsion is fed into the loop reactor as a liquid jet.

[0061] In preferred embodiments, the liquid jet fed into the liquid phase is directed upwards, preferably especially when the density of the particles is greater than the density of the liquid phase.

[0062] To solve the aforementioned problems (13) and (14), in preferred embodiments the immiscible reactants are fed into the liquid phase via the nozzle, preferably at the bottom of the loop reactor, over a specific period of time at the beginning of the reaction or even during the entire reaction. In this way, the immiscible reactants are The substances are mixed into a fine liquid-liquid dispersion. Additionally, the free circulation of the particles is driven by the momentum of the liquid jet.

[0063] In other preferred embodiments, the liquid jet injected into the liquid phase is directed downwards, preferably especially when the density of the particles is less than the density of the liquid phase.

[0064] A key advantage of the invention is that conventional reactors with an external liquid circuit, such as gas injection jet reactors used for hydrogenations, alkoxylations, esterifications, amidations, aminations, etc., can be retrofitted with the hydrodynamic loop reactor according to the invention without requiring major structural modifications. The hydrodynamic loop reactor according to the invention is integrated into the external liquid circuit of the existing reactor. After the conversion, the actual condensation reaction takes place in the hydrodynamic loop reactor, while the existing reactor can continue to be used as an expansion vessel for separating the process water. This results in a low investment threshold for the introduction of a new and highly sustainable production process.

[0065] As the reactants are converted under heterogeneous enzymatic catalysis, the desired reaction product accumulates in the liquid phase, preferably dissolved in the liquid phase or present in a mixture with the other components of the liquid phase.

[0066] It is also possible that the liquid phase is two-phase, preferably an emulsion, whereby both water-in-oil emulsions and oil-in-water emulsions are possible.

[0067] In order to remove the liquid phase together with the reaction product and by-product from the loop reactor without also removing particles, the loop reactor according to the invention includes a retention device.

[0068] The retention device can be designed, for example, as a filter, sieve or grid, with the liquid-permeable openings being smaller than the particles.

[0069] The retention device preferably serves not only to retain the particles in the loop reactor, but also to remove reaction product contained in the liquid phase and water as a byproduct from the loop reactor. For this purpose, the retention device is preferably operatively connected to a liquid outlet.

[0070] In preferred embodiments, the liquid outlet and retention device are arranged at the upper end of the loop reactor, preferably as, for example, a circular filter with a central outlet nozzle (Figure 3A).

[0071] In other preferred embodiments, the liquid outlet and retention device are arranged at the bottom of the loop reactor, preferably as, for example, a circular ring filter with an eccentric outlet nozzle (Figure 3B).

[0072] In further preferred embodiments, the liquid outlet and retention device are arranged in a downpipe of the loop reactor, preferably as, for example, a cylindrical filter with one or more outlet nozzles (Figure 3C). The advantage of a cylindrical filter in the annular downpipe is a larger available filtration area and cross-flow filtration. Both reduce the risk of filter clogging, which is particularly advantageous with small catalyst particles and extends maintenance intervals.

[0073] Preferably, the system also includes a separation device configured to separate by-product from the discharged liquid phase.

[0074] To solve problem (12), the apparatus according to the invention can include the separation device as a physically separate element for removing byproduct, preferably water. The removal of byproduct, preferably water, takes place after the liquid phase containing the reaction product and byproduct has been discharged from the loop reactor and the particles have been retained by the retention device in the loop reactor. If the discharged liquid phase containing the reaction product and byproduct is subsequently heated and sheared, no enzyme is present in suspended form in the discharged liquid phase and therefore cannot be denatured by heating and shearing.

[0075] Preferably, the loop reactor is configured for the conversion of the reactants at a reaction pressure (of, for example, greater than 1 bar (a)), wherein the separation device for the separation of by-product, preferably water, is configured at a separation pressure (of, for example, less than 1 bar (a)), and wherein the separation pressure is lower than the reaction pressure.

[0076] Preferably, the separation device comprises an expansion vessel and is configured for evaporating the byproduct, preferably water, suctioning off, and condensing the gas phase. In preferred embodiments, the separation device includes a spray device opening into an expansion vessel, wherein the spray device is preferably designed as a spray tube, a spray ring, or a Venturi nozzle. The spray device is preferably characterized by a large gas-liquid interface to achieve a high mass transfer rate of the byproduct, preferably water, from the discharged liquid phase into the gas phase and thereby maintain low concentrations of byproduct, preferably water, throughout the entire reaction and especially towards the end of the reaction.

[0077] Preferably, the separation device includes a device for supplying an inert gas.

[0078] Preferably, the inert gas is used to strip the byproduct, preferably water. The system preferably includes a condensation device to subsequently condense the byproduct, preferably water, driven off during stripping along with the inert gas and separate it from the inert gas.

[0079] Preferably, the system includes a return line, preferably to the inert gas injection device, in order to reuse the recovered inert gas, preferably in a closed system. An advantage of this concept is that the entire system, comprising the hydrodynamic loop reactor with the solid suspension contained therein and the expansion vessel of the separation device, can be operated in a closed system with inert gas circulation (e.g., N₂, Ar, etc.) without emissions. This is possible because the mixer for mixing the liquid phase with the inert gas, preferably a Venturi jet mixer, acts as a compressor for the inert gas circuit. Power is preferably supplied by a circulation pump.

[0080] Preferably, the heating device is configured to heat the discharged liquid phase comprising the reaction product and by-product.

[0081] Preferably, a heat exchanger and a heating device are arranged between the loop reactor and the separation device.

[0082] Preferably, the heat exchanger comprises an inlet / outlet exchanger and / or a trim cooler to set a higher temperature (preferably above 100°C) in the separation device for the removal of by-product, preferably water, and a lower temperature (preferably below 100°C) in the loop reactor with the suspended particles for the enzymatically catalyzed reaction, without compromising the energetic advantage of the enzymatically catalyzed reaction.

[0083] In preferred embodiments, the inventive system is designed as a closed-loop system. The by-product content is reduced in a separation device in the discharged liquid phase containing the reaction product and by-product. The remaining liquid phase containing the reaction product is then preferably returned to the loop reactor.

[0084] Preferably, a heat exchanger, preferably an inlet / outlet exchanger, is arranged downstream of the loop reactor in the flow direction of the liquid phase, and is configured to preheat the liquid phase.

[0085] Preferably, a heating device is arranged downstream of the heat exchanger in the flow direction of the liquid phase, which is configured to further heat the liquid phase.

[0086] Preferably, a separation device is arranged downstream of the heating device in the flow direction of the liquid phase, which is configured to separate by-product, preferably using inert gas (stripping).

[0087] Preferably, a circulation pump is arranged downstream of the separation device in the flow direction of the liquid phase.

[0088] Preferably, the heat exchanger is arranged downstream of the circulation pump in the flow direction of the liquid phase, preferably the inlet / outlet exchanger, which is configured to cool the liquid phase and transfer its heat to the liquid phase that is discharged from the loop reactor.

[0089] Preferably, a cooler, preferably a trim cooler, is arranged downstream of the heat exchanger in the flow direction of the liquid phase, which is configured to further cool the liquid phase.

[0090] Preferably, the mixer is arranged downstream of the cooler in the direction of flow of the liquid phase and is configured to feed the recirculated liquid phase back into the loop reactor.

[0091] In other preferred embodiments of the invention, the catalyst is any fluidizable catalyst on a support or without a support, in particular a non-enzymatic catalyst, e.g. a metal catalyst or a resin catalyst.

[0092] Another aspect of the invention relates to a plant described above for the conversion of at least two reactants in a condensation reaction to at least one reaction product and one by-product in a liquid phase, wherein the conversion takes place under heterogeneous non-enzymatic catalysis and wherein the plant comprises the following elements: - a hydrodynamic loop reactor configured to receive catalyst particles, wherein the particles are freely suspended in the liquid phase; - a mixer configured to mix the reactants outside the loop reactor; wherein the mixer includes a nozzle configured to inject a liquid jet comprising the mixed reactants into the liquid phase, such that the injected liquid jet causes free circulation of the particles in the liquid phase; and - a retention device configured to retain particles in the loop reactor during discharge of a liquid phase comprising reaction product and by-product from the loop reactor.

[0093] Another aspect of the invention relates to a process for converting at least two reactants in a condensation reaction to at least one reaction product and byproduct in a liquid phase under heterogeneous enzymatic catalysis, preferably using the apparatus described above according to the invention. All preferred embodiments of the apparatus according to the invention described above also apply accordingly to the process according to the invention. Conversely, all preferred embodiments of the process according to the invention described below also apply accordingly to the apparatus according to the invention.

[0094] The inventive procedure comprises the following steps: (a) Providing a hydrodynamic loop reactor containing an enzyme immobilized on particles, wherein the particles are suspended freely in the liquid phase; (b) Mixing the reactants outside the loop reactor and injecting a liquid jet comprising the mixed reactants into the liquid phase via a nozzle, wherein- where the injected liquid jet causes a free circulation of the particles in the liquid phase; and (c) Discharging a liquid phase comprising reaction product and by-product from the loop reactor, leaving the particles behind in the loop reactor.

[0095] Preferably, the reactants are mixed in step (b) immediately before the mixed reactants are fed into the loop reactor.

[0096] Preferably, at least one reaction product is selected from esters, amides, amines and etheme.

[0097] Preferably, the inventive method includes the additional step (d) Separation of by-product, preferably water, from the discharged liquid phase, preferably using the separation device described above.

[0098] Preferably, the reaction of the reactants takes place at a reaction pressure, wherein the separation of by-product, preferably water, takes place at a separation pressure, and wherein the separation pressure is lower than the reaction pressure.

[0099] Preferably, step (d) is carried out using a spray device opening into a pressure relief vessel, wherein the spray device is preferably designed as a spray tube, spray ring or as a Venturi nozzle.

[0100] Preferably, an inert gas is injected in step (d), preferably to increase the interface area.

[0101] Preferably, the temperature of the discharged liquid phase comprising reaction product and by-product is changed after discharge in step (c) and before separation in step (d).

[0102] Preferably, the extracted liquid phase is heated.

[0103] In preferred embodiments, the inventive process is carried out as a batch process.

[0104] In other preferred embodiments, the inventive method is carried out semi-continuously.

[0105] In further preferred embodiments, the inventive method is carried out continuously.

[0106] Figure 1 schematically shows a preferred embodiment of a system according to the invention. A liquid phase (1) is arranged in the reaction chamber of a hydrodynamic loop reactor (2). Particles (3) on which enzyme is immobilized are suspended in the liquid phase (1). The particles (3) circulate freely, as indicated by the arrows. Reactants are mixed together via a mixer (4), which can, for example, be designed as a Venturi mixer, and the resulting liquid jet (6) is injected into the reaction chamber of the reactor via a nozzle (5), preferably a Venturi nozzle. The liquid is fed into the loop reactor (2). The momentum of the liquid jet (6) causes the suspended particles (3) to circulate freely in the liquid phase (1). Alternatively, the mixer (4) can also be designed, for example, as a T-piece with a subsequent cone.

[0107] Since one of the reactants is either hydrophilic (and therefore harmful to the enzyme), or volatile under the conditions in the separation device, or immiscible with the first reactant, or should be present in a low concentration for other reasons, or should be dosed slowly, it is intended that this second reactant be introduced at least partially (semi-)continuously into the mixer (4) via the feeder (17). It is also possible to divide this reactant into partial streams for introduction into the mixer (4) and into the separation device (9) (via a device for feeding reactant 14).

[0108] At the upper end of the reaction chamber of the loop reactor (2) a retention device (7) is arranged, through which liquid phase (8) comprising reaction product and by-product is discharged, whereby the particles (3) are retained by the retention device (7) in the reaction chamber of the loop reactor (2).

[0109] The discharged liquid phase (8) is preferably passed through an inlet / outlet heat exchanger (1a), where it absorbs heat from a recirculated flow (preheating). The preheated discharged liquid phase (8) is then heated in a heating device (12). Subsequently, the heated discharged liquid phase (8) is mixed in a further mixer (16), preferably a Venturi nozzle mixer, with recirculated inert gas and optionally fresh inert gas, which is supplied via device (10). The mixture thus produced is introduced into a separating device (9).

[0110] In the separation device (9), by-product, preferably water, is discharged together with inert gas, and in a condensation device (15) the by-product, preferably water, is condensed and thus separated from the inert gas. The inert gas is returned to the further mixer (16). The separation device (9) has a device for feeding in a reactant (14), through which the first reactant is introduced.

[0111] In the illustrated embodiment, the heated liquid phase, from which a byproduct, preferably water, was separated in the separation device (9), is drawn in by a circulation pump (13) and returned as a recirculation flow to the inlet / outlet heat exchanger (11a), where it transfers heat to the discharged liquid phase (8) to preheat it. The recirculation flow is then preferably further cooled in a trim cooler (11b) before being returned to the mixer (4).

[0112] Figure 2 schematically shows a variant of the preferred embodiment of a plant according to the invention as shown in Figure 1. In this process, inert gas is fed into the liquid phase in the separation device (9) via device (10) and a second reactant is fed into the liquid phase via device (14). The liquid phase (8), heated in the heating device (12), is fed into the expansion vessel of the separation device via a (9) Discharge spray device, which is designed as a spray tube or spray ring, is fed to the separating device (9). The further mixer (16) according to Figure 1 is omitted.

[0113] Figure 3 schematically shows preferred embodiments for the arrangement of the retention device (7) in the loop reactor (2). In the preferred embodiment according to Figure 3A, the liquid outlet and retention device (7) are arranged at the upper end of the loop reactor (2), preferably as, for example, a circular filter with a central outlet nozzle. In the preferred embodiment according to Figure 3B, the liquid outlet and retention device (7) are arranged at the bottom of the loop reactor (2), preferably as, for example, a circular ring filter with an eccentric outlet nozzle. In the preferred embodiment according to Figure 3C, the liquid outlet and retention device (7) are arranged in a downpipe of the loop reactor (2), preferably as, for example, a cylindrical filter with one or more outlet nozzles.

[0114] Reference symbol list: 1 liquid phase 2-loop reactor 3 particles 4 mixers 5 nozzle 6 Liquid jet 7 Restraint device 8 discharged liquid phase 9 Separating device 10 Device for supplying inert gas 11 heat exchangers 11a Inlet / Outlet Exchanger 11b Trim cooler 12 Heating precautions 13 Circulation pump 14 Device for feeding the first reactant 15 Condensation device 16 more mixers 17. Feed for the second reactant

Claims

Patent claims:

1. A plant for the conversion of at least two reactants in a condensation reaction to at least one reaction product and one by-product in a liquid phase (1) under heterogeneous enzymatic catalysis, the plant comprising the following elements: - a hydrodynamic loop reactor (2) configured to accommodate an enzyme immobilized on particles (3), wherein the particles (3) are suspended freely in the liquid phase (1); - a mixer (4) configured to mix the reactants outside the loop reactor (2); wherein the mixer (4) comprises a nozzle (5) configured to inject a liquid jet (6) comprising the mixed reactants into the liquid phase (1), such that the injected liquid jet (6) causes free circulation of the particles (3) in the liquid phase (1); and - a retention device (7) configured to retain the particles (3) in the loop reactor (2) during discharge of a liquid phase (8) comprising reaction product and by-product from the loop reactor (2).

2. The system according to claim 1, wherein the liquid jet (6) fed into the liquid phase (1) is directed upwards; preferably wherein the density of the particles (3) is greater than the density of the liquid phase (1).

3. The system according to claim 1, wherein the liquid jet (6) fed into the liquid phase (1) is directed downwards; preferably wherein the density of the particles (3) is less than the density of the liquid phase (1).

4. The plant according to one of the preceding claims, which additionally comprises a separation device (9) configured to separate by-product from the discharged liquid phase (8).

5. The system according to one of the preceding claims, wherein the loop reactor (2) is configured for the conversion of the reactants at a reaction pressure, wherein the separation device (9) is configured for the separation of by-product, preferably water, at a separation pressure, and wherein the separation pressure is lower than the reaction pressure.

6. The system according to claim 5, wherein the separation device (9) comprises a pressure-reducing vessel and is configured for evaporating the by-product, preferably water, extracting and condensing the gas phase.

7. The system according to one of claims 4 to 6, wherein the separating device (9) comprises a spray device opening into a pressure vessel, wherein the spray device is preferably designed as a spray tube, a spray ring or a Venturi nozzle.

8. The system according to one of claims 4 to 7, wherein the separating device (9) comprises a device (10) for supplying an inert gas.

9. The system according to one of claims 4 to 8, wherein a heat exchanger (11) and a heating device (12) are arranged between the loop reactor (2) and the separation device (9).

10. The system according to claim 9, wherein the heating device (12) is configured to heat discharged liquid phase (8) comprising reaction product and by-product.

11. The system according to one of the preceding claims, wherein the nozzle (5) is a Venturi nozzle.

12. A process for converting at least two reactants in a condensation reaction to at least one reaction product and by-product in a liquid phase (1) under heterogeneous enzymatic catalysis, preferably using a system according to one of the preceding claims, wherein the process comprises the following steps: (a) Providing a hydrodynamic loop reactor (2) containing an enzyme immobilized on particles (3), wherein the particles (3) are suspended freely in the liquid phase (1); (b) Mixing the reactants outside the loop reactor (2) and injecting a liquid jet (6) comprising the mixed reactants into the liquid phase (1) via a nozzle (5), wherein the injected liquid jet (6) causes free circulation of the particles (3) in the liquid phase (1); and (c) Discharging a liquid phase (8) comprising reaction product and by-product from the loop reactor (2), leaving the particles (3) in the loop reactor (2).

13. The method according to claim 12, wherein the mixing of the reactants in step (b) takes place immediately before the mixed reactants are fed into the loop reactor (2). 19 240550P10WO 14. The method according to claim 12 or 13, wherein the at least one reaction product is selected from esters, amides, amines and ethems.

15. The method according to any one of claims 12 to 14, comprising the additional step (d) Separation of by-product, preferably water, from the discharged liquid phase (8) .

16. The method according to claim 15, wherein the reaction of the reactants takes place at a reaction pressure, wherein the separation of by-product, preferably water, takes place at a separation pressure, and wherein the separation pressure is lower than the reaction pressure.

17. The method according to claim 15 or 16, wherein step (d) is carried out using a spray device opening into a pressure vessel, wherein the spray device is preferably designed as a spray tube, spray ring or a Venturi nozzle.

18. The method according to one of claims 15 to 17, wherein in step (d) an inert gas is injected, preferably to increase the interface area.

19. The method according to any one of claims 15 to 18, wherein the temperature of the discharged liquid phase (8) comprising reaction product and by-product is changed after discharge in step (c) and before separation in step (d).

20. The method according to claim 19, wherein the discharged liquid phase (8) is heated.

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