Organic compound production method and production device

Abstract

Provided is a production method in which a useful organic compound is continuously concentrated, separated, and recovered with low energy. Also provided are a production method and a production device for concentrating, separating, and recovering a useful organic compound after membrane extraction of the organic compound from a solvent. This production method: includes a concentration step for using a reverse osmosis membrane to concentrate, by osmotically assisted reverse osmosis (OARO), an organic compound extracted into an organic solvent that does not contain water; and includes, as a pre-step before the concentration step, an extraction step for using a separation membrane to extract, into the organic solvent, an organic compound that has dissolved in a solvent A. This production device is provided with: a solvent A in which an organic compound has been dissolved; an organic solvent; a hollow fiber membrane; a configuration A in which the solvent A circulates outside the hollow fiber membrane; a configuration B in which the organic solvent circulates inside the hollow fiber membrane; a reverse osmosis membrane; and a configuration C in which the organic solvent, after having passed through the inside of the hollow fiber membrane, flows on the high-pressure side of the reverse osmosis membrane and branches into a concentrated solution and a reflux solution, and the reflux solution flows on the low-pressure side of the reverse osmosis membrane and circulates as a diluted solution.

Description

Organic compound manufacturing method and manufacturing device

[0001] The present invention relates to a method and apparatus for continuously concentrating, separating and recovering useful organic compounds (organic acids, aromatic compounds, fragrances, etc.) using low energy.

[0002] Methods such as extraction, distillation, and crystallization are known as methods for separating useful organic compounds dissolved in a solvent from the solvent they are dissolved in. For example, in bioproducts, which utilize the functions of microorganisms, animals, plants, etc. to produce organic compounds, the useful organic compounds exist in a very dilute state, so they need to be highly purified before use. However, because the useful organic compounds exist in a dilute state in the solvent, conventional techniques have the problem of requiring a great deal of energy for separation and concentration.

[0003] Furthermore, large-scale separation membranes used in industry are specialized for water treatment processes, and separation membranes for organic solvent separation have not been fully developed. For example, in the petrochemical industry, the development of organic solvent reverse osmosis (OSRO) membranes is being considered as separation membranes for alcohols and aromatic compounds. Furthermore, organic solvent nanofiltration (OSN) membranes are used in organic solvent recycling processes in the food and pharmaceutical industries (see, for example, Patent Document 1). However, new separation membranes with the necessary properties for organic solvent separation, such as organic solvent resistance, chemical resistance, and pressure resistance, are needed.

[0004] Non-Patent Document 1 discloses a continuous extraction process in which a culture medium and artificial green algae are allowed to interact with a dodecane solvent phase using a hollow fiber contactor with a microfiltration membrane to extract patchoulol produced by the algae, and then patchoulol is continuously extracted from the dodecane using methanol using a nanofiltration membrane, thereby concentrating patchoulol in the methanol solvent phase and recovering dodecane for reuse.

[0005] Furthermore, Non-Patent Document 2 discloses a method for extracting phenol from a liquid culture medium in which Pichia yeast (P. pastoris with phenol production pathway genes introduced) is cultured using a hollow fiber membrane contactor with the organic solvent tributyrin. Non-Patent Document 3 discloses the separation of toluene, pentane, hexane, and heptane from a methanol solution using an organic solvent reverse osmosis (OSRO) membrane. OSRO membranes are RO membranes specifically designed for organic solvents. In contrast, osmotically assisted reverse osmosis (OARO) membranes are RO membranes that place a medium with osmotic pressure on the secondary side and contact it with the liquid on the primary side through the membrane, thereby reducing the osmotic pressure difference across the membrane and enabling the solvent to permeate faster even with low pressure on the primary side. Furthermore, Non-Patent Document 4 discloses a hybrid membrane process combining osmotically assisted reverse osmosis (OARO) and reverse osmosis (RO) to further reuse water and nutrients from waste streams.

[0006] However, while conventional technologies can extract organic compounds from solvents containing water, they have difficulty extracting only organic substances from organic solvents, and commercially available separation membranes have the problem of being unable to withstand high concentrations of organic solvents for long periods of time, making continuous concentration, separation, and recovery extremely difficult. Therefore, there is a need for a method and apparatus that can separate and concentrate organic substances from organic solvents using a separation membrane that can withstand organic solvents, and that can perform extraction and concentration in a single process with lower energy (lower pressure) than conventional methods, without the need for distillation, crystallization, etc.

[0007] International Publication Pamphlet WO2023 / 127611

[0008] S. Overmans et al., Continuous extraction and concentration of secreted metabolites from engineered microbes using membrane technology, Green Chemical, 24, 5479 (2024).R. Kumokita et al., High-level phenol bioproduction by engineered Pichia pastoris in glycerol fed-batch fermentation using an efficient pertraction system, Bioresource Technology, 393 (2024) 130144.C. Liu et al., Organic solvent reverse osmosis membranes for organic liquid mixture separation: A review, 620 (2021) 118882.R. Gonzales et al., Hybrid osmotically assisted reverse osmosis and reverse osmosis (OARO-RO) process for minimal liquid discharge of high strength nitrogenous wastewater and enrichment of ammoniacal nitrogen, Water Research, 246 (2023) 120716.

[0009] The present inventors have succeeded in extracting useful organic compounds from a raw solution containing organic compounds using a separation membrane, extracting them from an organic solvent using a membrane with lower energy (lower pressure) than conventional methods, and concentrating and recovering the useful organic compounds to a desired concentration using an osmotically assisted reverse osmosis (OARO) method.

[0010] The present invention aims to provide a method for continuously concentrating, separating, and recovering useful organic compounds using low energy, and also to provide a method and apparatus for concentrating, separating, and recovering useful organic compounds after membrane extraction from a solvent.

[0011] To solve the above problems, the production method of the present invention provides the following [1] to

[11] , and the production apparatus of the present invention provides the following

[12] to

[13] . [1] A production method including a concentration step of concentrating an organic compound extracted into a water-free organic solvent using an osmotically assisted reverse osmosis (OARO) membrane. As used herein, the term "water-free organic solvent" refers to an organic solvent that does not contain water. However, since even commercially available organic solvents contain some water depending on their purity, and since organic solvents may contain moisture from the air when used in actual plant operation, this does not mean an organic solvent that is completely water-free, and it is acceptable for the organic solvent to contain 1% or less of water. [2] The production method of the above [1], in which the organic solvent is a lower alcohol such as methanol or ethanol. [3] The production method of the above [1], in which a pressure applied to the osmotically assisted reverse osmosis membrane is lower than the osmotic pressure of the organic solvent in which the organic compound is dissolved. [4] The production method of the above [1], in which the osmotically assisted reverse osmosis membrane is a hollow fiber membrane. [5] The production method according to any one of [1] to [4] above, further comprising an extraction step of extracting an organic compound soluble in solvent A into an organic solvent using a separation membrane. [6] The production method according to [5] above, wherein the organic solvent is capable of forming a separation interface with solvent A. [7] The production method according to [5] above, wherein the solubility of the organic compound in the organic solvent is greater than its solubility in solvent A. [8] The production method according to [5] above, wherein the separation membrane is an ultrafiltration membrane. [9] The production method according to [8] above, wherein the ultrafiltration membrane is a hollow fiber membrane.

[10] The production method according to [5] above, wherein the extraction step comprises a first extraction step of extracting the organic compound from solvent A with solvent B, and a second extraction step of extracting the organic compound from solvent B into an organic solvent, wherein the solubility of the organic compound in solvent B is greater than its solubility in solvent A and greater than its solubility in the organic solvent.

[11] The method according to any one of [1] to [4] above, wherein the organic compound is at least one selected from the group consisting of organic acids, aromatic compounds, flavorings, proteins, amino acids, vitamins, nucleic acids, and enzymes.

[12] A production apparatus comprising: a solvent A containing an organic compound dissolved therein; a water-free organic solvent; a hollow fiber membrane using a separation membrane; a configuration A in which solvent A is circulated outside the hollow fiber membrane; a configuration B in which the organic solvent is circulated inside the hollow fiber membrane; an osmotic pressure-assisted reverse osmosis membrane; and a configuration C in which, in configuration B, the organic solvent passes through the interior of the hollow fiber membrane and flows through the high-pressure side of the osmotic pressure-assisted reverse osmosis membrane, where it is branched into a concentrate and a reflux liquid, and the reflux liquid flows through the low-pressure side of the osmotic pressure-assisted reverse osmosis membrane and circulates as a diluent; the apparatus extracts the organic compound dissolved in solvent A into the organic solvent using the separation membrane, and concentrates the extracted organic compound using the osmotic pressure-assisted reverse osmosis membrane to recover the concentrate.

[13] The apparatus according to

[12] above, wherein configuration C includes a multi-stage membrane module using the osmotic pressure-assisted reverse osmosis membrane.

[14] A production method comprising an extraction step in which an organic compound dissolved in an aqueous or organic phase solvent is extracted into a water-free organic solvent using a separation membrane.

[15] The method according to

[14] above, wherein the organic solvent in the method according to

[14] above is diluted with an alcohol to a concentration of 20 to 50% by weight.

[16] The method according to

[15] above, wherein the alcohol in the method according to

[15] above is a higher alcohol having 5 or more carbon atoms in the molecule.

[0012] According to the present invention, useful organic compounds can be concentrated, separated and recovered continuously with low energy consumption.

[0013] Schematic diagram of the membrane extraction-membrane concentration manufacturing method Diagram of the hollow fiber membrane module Diagram of the concentration configuration using the partial reflux type osmotic pressure-assisted reverse osmosis (OARO) method Membrane extraction experimental system Experimental system for concentration using OARO membrane 1 Experimental results for concentration using OARO membrane 1 Experimental system and experimental results for concentration using OARO membrane 2 Graph showing the vapor pressure measurement results and osmotic pressure of benzoic acid (in MeOH solution) Diagram comparing batch processing and continuous processing in the extraction process Graft showing the concentration decrease curve of the aqueous phase malic acid concentration over time Graph showing the correlation between tri-n-octylamine (TOA) concentration and distribution coefficient

[0014] An example of an embodiment of the present invention will be described in detail below with reference to the drawings. Note that the scope of the present invention is not limited to the following examples and illustrated examples, and many modifications and variations are possible.

[0015] (1) Regarding Organic Compounds: In the present invention, organic compounds include organic acids, aromatic compounds, and flavorings. Here, organic acids are a general term for organic compounds that exhibit acidity, such as carboxylic acids having a carboxy group and sulfonic acids having a sulfo group. Specific examples include acetic acid, citric acid, lactic acid, malic acid, gluconic acid, tartaric acid, formic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, caproic acid, fumaric acid, and taurine. These compounds are used as seasonings in many processed foods and are also used as useful substances expected to have sterilizing, antibacterial, deodorizing, and antifungal properties. Furthermore, aromatic compounds are a general term for organic compounds that primarily contain a benzene ring, such as toluene, phenol, benzoic acid, xylene, cresol, phthalic acid, biphenyl, benzophenone, triphenylmethane, and naphthalene. Furthermore, a fragrance is a compound having an aroma, and refers to an organic compound or mixture for imparting a fragrance to foods, cosmetics, etc., and examples thereof include higher aliphatic hydrocarbons, terpene hydrocarbons, higher aliphatic alcohols, higher aliphatic aldehydes, ethers, esters, ketones, etc. Solvent A in the present invention is an aqueous phase or an organic phase, and contains the above-mentioned useful organic compound.

[0016] (2) Regarding Organic Solvents (2-1) When Solvent A is an Aqueous Phase When solvent A is an aqueous phase, the organic solvent used in the present invention must be an organic solvent that is substantially insoluble in water at room temperature. Specific examples include glycerin triesters to which a carboxylic acid having 3 to 12 carbon atoms is bonded, phosphate esters to which an alcohol having 3 to 12 carbon atoms is bonded, and dodecane, a linear alkane having 12 carbon atoms. Examples of glycerin triesters that can be preferably used include glycerin, lauric acid, undecenoic acid (having 12 carbon atoms), capric acid (having 10 carbon atoms), caprylic acid (having 8 carbon atoms), tributyrin (glycerol tributyrate), and tripropionin (glycerol tripropionate). All of these are used as organic solvents that are substantially insoluble in water at room temperature.

[0017] (2-2) When Solvent A is an Organic Phase In this case, the condition of being substantially insoluble in water at room temperature is not required, and any organic solvent can be used as long as it is immiscible with the organic phase of Solvent A through a separation membrane such as an ultrafiltration membrane. As the organic solvent, for example, an alcohol having 1 or 2 carbon atoms (e.g., methanol, ethanol) can be used.

[0018] In the production method of the present invention, in the extraction step performed as a pretreatment for the concentration step, organic compounds dissolved in solvent A are extracted into an organic solvent using a separation membrane. Microfiltration membranes (MF membranes) and ultrafiltration membranes (UF membranes) can be used as this separation membrane. The following describes ultrafiltration membranes. (3) Regarding Ultrafiltration Membranes: Ultrafiltration membranes have a pore size of 5 to 100 nm or a nominal molecular weight cutoff of 5 to 1,000 kD, which is larger than reverse osmosis membranes (RO membranes, NF membranes) but smaller than microfiltration membranes (MF membranes). These membranes are called UF (ultrafiltration membrane) membranes. Examples of materials that can be used for the ultrafiltration membrane in the present invention include cellulose, cellulose ester, aromatic polyamide, polyvinyl alcohol, polyethersulfone, polysulfone, polyvinylidene fluoride, polyacrylonitrile, ceramic, polycarbonate, and sulfonated polyethersulfone. For ease of handling, organic materials are preferred for the ultrafiltration membrane. The hydrophilic organic material is preferably polysulfone or polyethersulfone. As for the shape of the membrane, a flat membrane or a hollow fiber membrane is used, with the hollow fiber membrane being particularly preferred for continuous extraction.

[0019] The function of the ultrafiltration membrane in the present invention is to extract and separate useful organic compounds from solvent A (aqueous phase or organic phase) into an organic solvent by forming a separation interface between solvent A and the organic solvent inside the pores of the ultrafiltration membrane, thereby physically stabilizing the interface and forming such a separation interface over the entire membrane surface, thereby significantly increasing the surface area of ​​the interface and dramatically increasing the rate at which useful organic compounds transfer from solvent A to the organic solvent via the ultrafiltration membrane.

[0020] Any ultrafiltration membrane that can be used in the present invention can be used, regardless of its physical shape or chemical composition, as long as it can be used for the purpose of separating useful organic compounds from solvent A. For example, it is necessary for the useful organic compounds present in solvent A to migrate into the organic solvent through the ultrafiltration membrane, and therefore the membrane must have pores. The size and number of pores can be selected appropriately depending on the type of solvent used and the type of useful organic compound.

[0021] The hollow fiber ultrafiltration membrane of the present invention (hereinafter sometimes simply referred to as the hollow fiber membrane) may be subjected to a surface treatment to prevent deterioration during use. When the hollow fiber membrane comes into contact with an organic solvent, the organic solvent may penetrate into the material constituting the hollow fiber membrane, causing the hollow fiber membrane to swell or partially dissolve. As a result, the strength of the hollow fiber membrane may decrease, making it difficult to use continuously for long periods of time. Alternatively, the organic solvent may leak into the solvent A side. To improve the surface properties of such hollow fiber membranes, it is preferable to subject the ultrafiltration membrane surface to a hydrophilic treatment. The hydrophilic treatment improves the resistance of the hollow fiber membrane to organic solvents and prevents the organic solvent from passing through the membrane and leaking.

[0022] One method for hydrophilizing the interface between a hollow fiber membrane and an organic solvent is to blend various hydrophilic materials with the membrane-forming material during hollow fiber membrane production. Preferred hydrophilizing materials that can be used for this purpose include hydrophilic polymers such as polyvinylpyrrolidone and hydrophilic inorganic materials such as colloidal silica. Alternatively, the hydrophilic material can be exposed on the membrane surface after the hollow fiber membrane is formed by coating. Alternatively, when the hollow fiber membrane is made of a polymeric material, copolymers can be produced using various known methods and used. In this case, the hydrophilizing material can be a random copolymer, block copolymer, graft copolymer, or the like formed using vinylpyrrolidone, acrylic acid, 2-hydroxyethyl acrylic acid, acrylamide and its derivatives, vinyl acetate, or other hydrophilic monomers or copolymer monomers that can be hydrophilized by hydrolysis or other methods.

[0023] As other hydrophilization treatments, various plasma treatments are also preferably used. In this case, the plasma treatment method is preferably a low-temperature plasma treatment method, and a method in which plasma generated between high-voltage electrodes under atmospheric pressure is brought into contact with the film surface to perform hydrophilization treatment is particularly preferred. In addition, it is also preferred to perform a hydrophilization treatment on the film surface by vacuum plasma or low-temperature spraying of various ceramics, metals, etc.

[0024] Examples of materials constituting the hollow fiber membrane of the present invention include at least one selected from various polymers, ceramics, and metals, and are preferably used, which have good water resistance and chemical resistance, excellent mechanical strength, and excellent pressure resistance and heat resistance. In particular, organic polymer-based materials that are easy to mold are preferred. More specifically, the membrane material is preferably composed primarily of at least one selected from polyvinylidene fluoride, cellulose, polyolefin, polysulfone, polyethersulfone, polyvinyl chloride, polytetrafluoroethylene (PTFE), polyetherimide, and ceramic.

[0025] The hollow fiber membrane used in the present invention is preferably a cylindrical or fibrous separation membrane with a hollow center, with a longitudinal length of 50 to 2000 mm and an average outer diameter of 0.4 to 10 mm. The inner diameter of the hollow fiber membrane is preferably 0.3 to 9.5 mm. The substantive layer sandwiched between the outer surface and inner diameter of the hollow fiber membrane forms a porous structure with a porosity of preferably 5 to 90%, more preferably 30 to 90%, and the pore diameter of the outer surface of the porous structure exposed to the outer surface of the hollow fiber membrane is preferably 5 to 100 nm, and the pore diameter of the inner surface exposed to the inner diameter of the inner surface is preferably 5 to 100 nm. The sizes of the pores exposed on the surface and the inner surface may be the same or different, the pore size on the outer surface may be smaller than the pore size on the inner surface, and the mesh structure forming the separation layer may be formed with a mesh density that grades from dense to sparse or vice versa from the outer surface to the inner surface. Here, solvent A and the organic solvent may be disposed either outside or inside the hollow fiber membrane. That is, by disposing solvent A in the internal flow path of the hollow fiber membrane and disposing the organic solvent on the outer surface of the hollow fiber membrane, it is possible to efficiently extract useful organic compounds. Alternatively, it is also possible to dispose the organic solvent in the internal flow path of the hollow fiber membrane and extract and separate useful organic compounds from solvent A outside the hollow fiber membrane into the organic solvent inside the hollow fiber membrane.

[0026] The hollow fiber membrane of the present invention has a substance layer having a pore size and porosity within the above-mentioned ranges. However, it is preferable to optimize the pore size and porosity to prevent leakage of the organic solvent into solvent A and to increase the extraction efficiency of useful organic compounds. For this purpose, additives can be added to the materials used to produce the hollow fiber membrane to control the pore size and porosity of the substance layer. Various known soluble pore-forming agents can be used as additives. Examples of such additives include inorganic salts such as table salt, sugars such as sucrose, and polymer particles such as acrylic or styrene-based polymer particles and silicone-based particles such as colloidal silica, which are particles whose size and shape can be controlled in advance. Alternatively, non-solvent-induced phase separation (NIPS) or thermally induced phase separation (TIPS) can be used to produce hollow fiber membranes with various pore sizes and porosities by combining two or more incompatible polymers to induce a phase-separated structure, and selectively dissolving and removing one of the polymer components. A wide variety of incompatible, dissolvable polymers are available for this purpose.

[0027] A single hollow fiber membrane or multiple hollow fiber membranes may be used. When multiple hollow fiber membranes are used, they may be arranged in parallel to each other and bundled together, and the hollow fiber membranes may be arranged in contact with each other or at appropriate intervals.

[0028] In a process for separating useful organic compounds from solvent A using a hollow fiber membrane, an organic solvent that dissolves the organic compound and is immiscible with solvent A is used, and solvent A and the organic solvent are separated through the hollow fiber membrane, thereby extracting and separating the organic compound from solvent A into the organic solvent. The organic solvent used must be substantially insoluble in solvent A at room temperature to prevent mixing and emulsification of solvent A and the organic solvent when they come into contact with each other through the hollow fiber membrane. Solvent A and the organic solvent may be located either inside or outside the hollow fiber membrane. In either case, the extraction efficiency of the organic compound can be improved by adjusting the flow rate of the fluid flowing inside the hollow fiber membrane or by adjusting the pressure inside or outside the hollow fiber membrane. The hollow fiber membrane may be used with both the supply side and the permeation side of the internal liquid open, or with one permeation side sealed with potting. The hollow fiber membrane can be used as an integrated separation device in a module. For example, as shown in the examples described later, a method may be used in which a hollow fiber membrane module is prepared by bundling a plurality of hollow fiber membranes, an organic solvent is introduced into the hollow fiber membranes, and solvent A is disposed on the outside of the hollow fiber membranes inside the module.

[0029] In a preferred embodiment of the present invention, the organic solvent introduced into the hollow fiber is circulated by a pump, and solvent A and the organic solvent are continuously contacted via the hollow fiber membrane, thereby enabling separation of useful organic compounds. When solvent A is disposed inside the hollow fiber membrane, various insoluble components generated in solvent A may cover the surface of the hollow fiber membrane, causing clogging of the pores and preventing diffusion of the useful organic compounds. In contrast, a system in which the organic solvent is disposed inside the hollow fiber membrane is preferred because clogging of the hollow fiber membrane is less likely to occur. In this case, it is preferable to circulate the organic solvent inside the hollow fiber membrane by a pump or the like in order to separate useful organic compounds more efficiently.

[0030] (4) Osmotically Assisted Reverse Osmosis (OARO) The OARO process is an application of the RO process, using separation membranes with pore sizes of 2 nm or less. In the RO process, a feed solution is passed through one side of the membrane, and water is permeated by applying a pressure equal to or greater than the osmotic pressure of the feed solution. In contrast, the OARO process involves passing two solutions with similar salt concentrations and osmotic pressures, one on the high-pressure side and the other on the low-pressure side of a semipermeable membrane, and applying pressure to one side to obtain a concentrated solution and a diluted solution. The OARO process minimizes the osmotic pressure difference on both sides of the membrane, significantly reducing the operating pressure required for the feed solution to permeate the membrane. Similar to the RO process, the OARO process achieves membrane permeation by applying a pressure higher than the osmotic pressure difference on both sides of the membrane.

[0031] As with the RO process, the membranes that can be used in the OARO process are of two types: flat membranes and hollow fiber membranes. The membrane material is preferably a material containing at least one of a cellulose-based resin, a polysulfone-based resin, and a polyamide-based resin. The cellulose-based resin is preferably a cellulose acetate-based resin, more preferably cellulose acetate, and from the viewpoint of durability, cellulose triacetate is even more preferable. The polysulfone-based resin is preferably a polyethersulfone-based resin, more preferably sulfonated polyethersulfone.

[0032] Here, membrane separation using the OARO method will be described with reference to FIG. 3(1). In the OARO method, a feed solution 36 (high-pressure side solution) is applied with a feed pump 35 at a first pressure to flow into the first chamber 33a (high-pressure side), and a reflux solution 38 (low-pressure side solution) is passed through the second chamber 34a at a second pressure lower than the first pressure. This causes the solvent contained in the feed solution in the first chamber 33a to migrate through the separation membrane 32a to the reflux solution in the second chamber 34a. This results in a concentrated solution (a concentrated feed solution) being discharged from the first chamber 33a, and a diluted solution (a diluted reflux solution) being discharged from the second chamber 34a. This allows the feed solution to be concentrated and the reflux solution to be diluted. While the above description was based on the feed solution and the reflux solution using FIG. 3(1), the same applies to separate solutions. Although the separation membrane 32a is depicted as a flat membrane in Fig. 3(1) for simplification, it is assumed that the separation membrane 32a is a hollow fiber membrane or a flat membrane. In particular, a hollow fiber membrane can increase the membrane area per unit volume of the membrane module, thereby increasing the membrane permeation flow rate per unit volume of the membrane module.

[0033] In addition, the OARO process can increase the concentration of concentrate to near saturation by using a multiple-unit configuration. Figure 3(1) shows a five-unit OARO membrane module configuration, in which a portion of the concentrate 37 obtained from the feed liquid 36 via the five OARO membrane modules is refluxed as reflux liquid 38, and is finally discharged as dilute liquid 39. In Figure 3(1), 40, 41, and 45 are pressure gauges, 46 is a flow meter, 42 is a backpressure valve, and 43 and 44 are flow control valves. Note that while a five-unit OARO membrane module configuration is shown here, this is just one example.

[0034] As shown in Figure 3(2), the concentration increases through each of the first to fifth OARO membrane modules (32a to 32e), and a portion of the concentrate 37 finally obtained is refluxed as reflux 38, which flows through the fifth, fourth, ..., first modules and is discharged from the first module as diluted solution 39. The separation membranes (OARO membrane modules) in each module minimize the osmotic pressure difference on both sides of the membrane, significantly reducing the operating pressure required to permeate the membrane.

[0035] The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. In the examples, percentages are by weight unless otherwise specified.

[0036] (Preparation of hollow fiber ultrafiltration membrane) N,N-dimethylacetamide (DMAC) was used as a solvent, and 18 parts of polyvinylidene fluoride (PVDF; Arkema (registered trademark) Kynar) and 2 parts of polyvinylpyrrolidone (PVP; K-30; Fujifilm Wako Pure Chemical Industries, Ltd.) were added to 80 parts of DMAC and left overnight at room temperature to obtain a uniformly dissolved solution. To prepare the hollow fiber membrane, a non-solvent-induced phase separation method (NIPS method) was used, and a PVDF solution containing PVP was introduced into the outer periphery of a double-tube nozzle, and at the same time, ion-exchanged water was introduced as a coagulation liquid into the central outlet of the double-tube nozzle. While the PVDF solution and the coagulation liquid (ion-exchanged water) were simultaneously discharged from the double-tube nozzle, the hollow fiber membrane composed of the precipitated PVDF / PVP blend membrane was introduced into a coagulation bath filled with water adjusted to 40 ° C., and then wound up, and then wound up from the coagulation bath using a roller and onto a winder drum. The air gap between the tip of the double-tube nozzle and the water surface of the coagulation bath was set to 15 cm, and the winding speed was set to 5.5 m / min.

[0037] The wound hollow fiber membrane sample was immersed in tap water for 2 days, and then in a 50% glycerin solution at room temperature for 3 days to remove soluble components from the membrane. The glycerin was then removed and the membrane was thoroughly dried at room temperature. The resulting hollow fiber membrane had an outer diameter of 2.2 mm, an inner diameter of 2.0 mm, and an effective thickness of 0.1 mm.

[0038] The average thickness of the hollow fiber membrane's substantive layer is 0.2 mm, and the interior of the substantive layer forms a mesh structure with pores averaging approximately 50 μm in size. The outer surface of the hollow fiber membrane is covered with a dense skin layer. Voids are formed below the skin layer, which connect to the large mesh structure inside the substantive layer and further connect to voids formed on the inner surface of the hollow fiber membrane, leading to the porous membrane on the inner surface. The porosity of the substantive layer, calculated from the ratio of the mass and volume of the substantive layer, was approximately 87%.

[0039] The average diameters of the pores formed on the outer and inner surfaces of the hollow fiber membrane were 37 nm and 63 nm, respectively. The outer surface of the hollow fiber membrane forms an ultrafiltration membrane with minute pores.

[0040] (Preparation of hollow fiber membrane module) The hollow fiber membranes prepared in Example 1 were used and cut to a length of 30 cm. 10 to 30 hollow fiber membranes were bundled together and fixed in a tube with both ends open using an isocyanate adhesive. Two openings were provided in the tube, perpendicular to the longitudinal direction of the hollow fiber membranes, providing a structure that allowed the circulation of solvent A. Figure 2 shows a structural diagram of the hollow fiber membrane module prepared in this example.

[0041] As shown in Figure 2, the hollow fiber membrane module (20) is configured such that bundled hollow fiber membranes are connected at both ends to separate tube piping connected to the outside via connectors (21a, 21b), and organic solvents (18a, 18b) in external containers are circulated inside the hollow fiber membranes. An inlet opening (22a) and an outlet opening (22b) are provided outside the hollow fiber membranes in the hollow fiber membrane module (20) so that solvent A (11) can be circulated. The useful organic compound (12) enters the organic solvent inside the hollow fiber membranes from solvent A (11) outside the hollow fiber membranes in the hollow fiber membrane module (10). In the fabricated hollow fiber membrane module, the volume fraction occupied by the hollow fiber membranes in the hollow fiber membrane module was 44%, and the surface area of ​​the hollow fiber membranes was 213 cm. ３ It was.

[0042] (OARO membrane module) A commercially available OARO membrane module was used to examine the pressure resistance in the OARO process for concentrating organic compounds in organic solvents. Under the conditions of the study, a single hollow fiber or flat membrane OARO membrane module was used to concentrate 20 wt% benzoic acid in MeOH solution using the OARO process.

[0043] (1) OARO membrane module 1 (HOLLOSEP Mini (registered trademark), manufactured by Toyobo MC Co., Ltd.; for details, see the URL https: / / www.toyobo-mc.jp / products / hollosep_mini / ) (1-1) Two-sided liquid supply method As shown in Figure 5 (1-1), 20 wt% benzoic acid (in MeOH solution) was supplied to the outside of the hollow fiber at a flow rate of 6 mL / min and a pressure of 5 MPa, and 20 wt% benzoic acid (in MeOH solution) was supplied to the inside of the hollow fiber at a flow rate of 2.5 mL / min and a pressure of 0.3 MPa. As a result, about 1 hour after the start, the pressure of the liquid supplied to the inside of the hollow fiber increased from 0.3 to 3.5 MPa, but thereafter the inside pressure was maintained, and the transmembrane pressure difference (the difference between the outside pressure and the inside pressure of the membrane module) was 1.5 MPa. That is, at the beginning, the transmembrane pressure (driving force) was about 5 MPa, but after about 1 hour, the transmembrane pressure dropped to about 1.5 MPa (5-3.5). However, as shown in Figure 6 (1-1), the concentration of benzoic acid was concentrated from 20 wt% at the start to 21.7 wt% at the outer outlet after 20 hours, and the inner outlet concentration was diluted to 18.0 wt%. This means that 20 wt% benzoic acid (in MeOH solution) was successfully concentrated by the OARO method at a transmembrane pressure of 1.5 MPa.

[0044] (1-2) Partial Reflux Method As shown in Figure 5 (1-2), 20 wt% benzoic acid (in MeOH solution) was supplied to the outside of the hollow fiber at a flow rate of 6 mL / min and a pressure of 5 MPa, and a portion of the concentrated solution was refluxed and supplied to the inside of the hollow fiber. In this case, the dilute solution side was at approximately atmospheric pressure, and there was a transmembrane pressure difference (driving force) of approximately 5 MPa. However, as with the two-sided liquid feed method, after approximately 1 to 2 hours, the transmembrane pressure difference decreased to approximately 1.5 MPa. As a result, as shown in Figure 6 (1-2), the benzoic acid concentration increased from 20 wt% at the start to 22.2 wt% in the concentrated solution and 18.4 wt% in the diluted solution after 18 hours. 20 wt% benzoic acid (in MeOH solution) was successfully concentrated by the OARO method using partial reflux at a transmembrane pressure difference of 1.5 MPa. To concentrate benzoic acid (in MeOH solution) using the OARO membrane module 1, the pressure was increased to 5 MPa, but the pressure on the low-pressure side rose in a short time, and the effective transmembrane pressure difference was only 1.5 MPa. However, the concentrated solution of 20 wt % benzoic acid (in MeOH solution) became approximately 22 wt %.

[0045] (2) OARO membrane module 2 (manufactured by Nitto Denko Corporation, SWC4; for details, see the URL https: / / membranes.com / wp-content / uploads / Documents / Element-Specification-Sheets / RO / SWC / SWC4-LD.pdf). As shown in Figure 7(1), 20 wt% benzoic acid (in MeOH solution) was passed through a flat membrane (membrane area 7.55 cm) at a flow rate of 2 mL / min without pressure, with a liquid volume of 200 mL. ２The membrane was then fed to the upper side (nonwoven fabric side) of the flat membrane, and 20 wt% benzoic acid (in MeOH solution) was fed to the lower side (active layer side) of the flat membrane at a flow rate of 10 mL / min and a pressure of 3 MPa (200 mL). Then, the lower side was pressurized and concentrated using the OARO method (the transmembrane pressure was the difference between the lower and upper pressures). As shown in Figure 7 (2), the benzoic acid concentration increased from 20 wt% at the start of the OARO method to 24.9 wt% after 23 hours, and the diluted solution was diluted to 17.3 wt%. It was confirmed that 20 wt% benzoic acid (in MeOH solution) could be concentrated to 25 wt% by OARO concentration using the flat membrane of OARO membrane module 2. Further concentration is possible by increasing the membrane area.

[0046] For reference, the osmotic pressure of a 20 wt% benzoic acid solution (in MeOH solution) was measured. Figure 8(1) shows the vapor pressure measurement results for 0-30 wt% benzoic acid (in MeOH solution), and Figure 8(2) is a graph showing the osmotic pressure for 0-30 wt% benzoic acid (in MeOH solution). Vapor pressure measurements were performed on solutions with different benzoic acid concentrations, and the osmotic pressure was estimated from the measurements. The osmotic pressure of 20 wt% benzoic acid (1.47 mol / L) is approximately 3.5 MPa (35 bar). This means that a solution with an osmotic pressure of 3.5 MPa could be concentrated at a transmembrane pressure of 3 MPa or less using the OARO process with OARO membrane module 2. Note that, in principle, the RO process cannot concentrate a solution with an osmotic pressure of 3.5 MPa at a transmembrane pressure lower than that.

[0047] (Extraction Process) A schematic diagram of the experimental system for the extraction process and concentration process in this example is shown in Figure 1. First, the extraction system (10) includes a hollow fiber membrane module (20), an organic solvent (17) circulating inside the hollow fiber ultrafiltration membrane in the module, and a solvent A (11) circulating outside the hollow fiber ultrafiltration membrane in the module. Each liquid is stirred in its respective container (13, 18) and pumped by pumps (15, 19), with the flow rate and pressure of the liquid measured by a flow meter (not shown) and a pressure gauge (not shown), respectively. Note that the arrangement of the pumps is not limited to these arrangements.

[0048] As shown in Figure 9, in the case of batch processing, the liquid concentration on the extraction side increases over time, so the difference in chemical potential decreases over time and the extraction capacity decreases. In contrast, in the case of continuous processing such as the extraction process of this example, the concentration on the extraction side is kept constant, so the difference in chemical potential is also kept constant and the extraction capacity is maintained.

[0049] (Concentration Step) Next, in the concentration system (30), the organic compounds extracted into the organic solvent are concentrated using the OARO method. A feed solution 36 containing the extracted organic compounds (e.g., benzoic acid) in the organic solvent 17 (e.g., MeOH) is applied with a slightly higher pressure (first pressure) by a liquid pump 35 and flows into the first chamber 33 (high-pressure side). A portion of the feed solution is refluxed from the outlet, resulting in a reflux solution 38, which flows into the second chamber 34 at a second pressure lower than the first pressure. This transfers the organic solvent contained in the feed solution in the first chamber 33 to the reflux solution 38 in the second chamber 34 via the separation membrane 32. This allows the concentrated solution 37 to be discharged from the first chamber 33, and the diluted solution 39 to be discharged from the second chamber 34. The diluted solution 39 flows into the extract side (organic solvent 17) of the extraction system (10) (arrow B) and circulates between the extraction system and the concentration system. This allows for a continuous purification (production) process using membrane extraction and membrane concentration.

[0050] (Membrane Extraction Experimental Results) Experimental results for membrane extraction of benzoic acid as an organic compound are described with reference to Figure 4. First, an aqueous benzoic acid solution (initial concentration 0.25 wt%) was extracted with dodecane using a hollow fiber ultrafiltration membrane (hereinafter referred to as a hollow fiber membrane module). After dodecane was extracted, the concentration of benzoic acid (in dodecane) was 0.0116 wt%, and 0.133 wt% benzoic acid (in methanol solution) was extracted using methanol as an organic solvent. When the organic compound is an organic acid, ketones or hexane are preferably used as the organic solvent for extraction.

[0051] This example will focus on the extraction process. The extraction system (10) shown in FIG. 1 includes a hollow fiber membrane module (20), an organic solvent (17) circulating inside the hollow fiber ultrafiltration membrane within the module, and a solvent A (11) circulating outside the hollow fiber ultrafiltration membrane within the module. In this example, a hydrophilic cellulose diacetate (CA) hollow fiber membrane module (hereinafter also referred to as a CA membrane module) was used as the hollow fiber membrane module (20), and an experiment was conducted to extract malic acid using an aqueous malic acid solution as the solvent A and tri-n-octylamine (TOA) as the organic solvent (17). A non-solvent-induced phase separation method was used to produce the hollow fiber membrane. Here, cellulose diacetate refers to cellulose acetate synthesized by chemically treating wood pulp as a raw material. In addition to TOA, saturated hydrocarbon amine compounds with a molecular weight of 80 or more, such as n-pentylamine and n-octylamine, as well as compounds such as tributyl phosphate and tributyrin, are also effective as organic solvents (17) for extraction. Experiments on membrane extraction were conducted by varying the TOA ratio in the extraction solution, and the partition coefficient (D) and overall mass transfer coefficient (K) were calculated for the extraction efficiency under each experimental condition. ａ The evaluation was performed using the following formula:

[0052] Figure 10 shows the results of membrane extraction of malic acid in the aqueous solution (aqueous phase) using a CA membrane module, in which a 1 wt% malic acid aqueous solution was contacted with a 1-octanol solution of TOA. Figure 10 is a graph showing the concentration decrease curve of the aqueous phase malic acid over time (a solution with a TOA to 1-octanol ratio of 3:7, i.e., a TOA concentration of 30 wt%). In addition to 1-octanol, other higher alcohols with five or more carbon atoms in the molecule, such as 1-pentanol, 1-hexanol, 1-decanol, 1-dodecanol, and oleyl alcohol, are also effective as higher alcohols for diluting TOA. As shown in Figure 10, the malic acid concentration in the aqueous solution decreased over time due to contact between the aqueous solution and the extraction solution via the CA membrane module. It was found that the concentration reached equilibrium after approximately 50 hours. Overall mass transfer coefficient K ａwas calculated using the following formula from the concentration decrease curve of the malic acid concentration in the aqueous phase versus time. ａ = 1.77 x 10 -6 [m / s].

[0053]

[0054] In the above formula 1, Q ａ is the flow velocity of the aqueous phase [m ３ / s], Q ｏ is the extraction rate [m ３ / s], V ａ is the amount of water phase liquid [m ３ ], V ｏ is the volume of extracted liquid [m ３ ], S is the membrane area of ​​the membrane module [m ２ ], D is the partition coefficient, C ａ in (t) is the aqueous phase concentration at time t [g / m ３ ], K. ａ is the overall mass transfer coefficient [m / s].

[0055] The distribution coefficient of malic acid was determined by measuring the malic acid concentration in the aqueous phase when equilibrium was reached after membrane extraction had continued for 50 hours or more. The miscibility of the extraction phase liquid with the aqueous phase could not be confirmed by visual observation until the end of the extraction experiment. The dependence of the distribution coefficient and overall mass transfer coefficient measured in this manner on the TOA concentration is shown in the correlation graph of TOA concentration and distribution coefficient in Figure 11. The distribution coefficient reached its maximum value when the TOA concentration was 30 wt%. It was also found that the distribution coefficient was generally 50 or more when the TOA concentration was 20 to 50 wt%. The overall mass transfer coefficient K ａ These evaluation results showed that extraction using the CA membrane module proceeded efficiently without mixing of the extraction phase liquid with the aqueous phase when the ratio of TOA to 1-octanol was in the range of 1:4 to 1:1, and particularly preferably 3:7.

[0056] Here, we will explain the method for fabricating a CA membrane module. First, cellulose acetate is dissolved in N-methyl-2-pyrrolidone (7 parts) and tetraethylene glycol (3 parts) in a tank to prepare an 18 wt% solution. The dissolved solution is then extruded through a double-walled nozzle using a gear pump and introduced into a coagulation bath where it is coagulated to produce a hollow fiber membrane. Water is used as the internal liquid and coagulation liquid. The wound hollow fiber membrane is washed, and then the adhering water is replaced with a 50% aqueous glycerin solution and dried at room temperature. The fabricated hollow fiber membrane is cut to an appropriate length, both ends are sealed with epoxy resin, and the membrane is placed in a cylindrical plastic shroud to produce an external CA membrane module. An external membrane module is a device installed outside a reactor and pressurized by a pump to transfer solutes between the solvent circulating inside the membrane and the solvent circulating outside the membrane. In this example, a CA membrane was used as the hollow fiber membrane module, but other membranes such as a SPES (sulfonated polyethersulfone) membrane can also be used. However, PP (polypropylene) and Teflon (registered trademark) membranes, which are generally used for membrane separation, are not suitable because the organic phase leaks into the aqueous phase.

[0057] This technology can be widely used to purify useful organic compounds dissolved in aqueous systems produced in biomanufacturing processes using microorganisms or bioreactors that utilize enzymes, as well as to purify and concentrate organic compounds such as organic acids, aromatic compounds, and fragrances produced by conventional chemical synthesis.

[0058] 1 Manufacturing equipment 10 Extraction system 11 Solvent A 12 Organic compound 17, 18a, 18b Organic solvent 13, 18 Agitator 15, 19, 35 Liquid transfer pump 20 Hollow fiber membrane (ultrafiltration membrane) module 21a, 21b Connector 22a Inlet side opening 22b Outlet side opening 30 Concentration system 32, 32a to 32e Separation membrane (OARO membrane module) 36 Extract 37 Concentrated liquid 38 Reflux liquid 39 Diluted liquid 40, 41, 45 Pressure gauge 46 Flow meter 42 Back pressure valve 43, 44 Flow rate adjustment valve

Claims

1. An extraction step in which a solvent A in which a specific organic compound is dissolved is continuously flowed through one space of a separation membrane, and an organic solvent B is continuously flowed through the other space of the separation membrane, thereby forming an interface between the solvent A and the organic solvent B via the separation membrane and dissolving the organic compound in the organic solvent B, A concentration step is performed to obtain the organic solvent B in which the organic compound has been dissolved in the extraction step, by continuously supplying the organic solvent B with osmotic pressure assistance to an osmotic reverse osmosis membrane, thereby increasing the concentration of the organic compound. A method for producing the organic compound concentrated in the organic solvent B comprising the above-mentioned organic solvent B.

2. The manufacturing method according to claim 1, comprising a membrane module having, in the concentration step, a first chamber in which the organic solvent B is continuously supplied and the organic solvent B in which the concentration of the organic compound has increased is discharged, and a second chamber installed next to the first chamber via the osmotic pressure-assisted reverse osmosis membrane in which the organic solvent B in which the concentration of the organic compound has decreased moves from the osmotic pressure-assisted reverse osmosis membrane and the moved organic solvent B is discharged.

3. The manufacturing method of claim 2, wherein the organic solvent B discharged from the second chamber is supplied to the other space side of the separation membrane.

4. The manufacturing method of claim 2 or 3, wherein a portion of the organic solvent B, in which the concentration of the organic compound discharged from the first chamber has increased, is supplied to the second chamber.

5. The manufacturing method of claim 2, wherein the membrane module is formed in multiple stages.

6. The method for producing the product according to claim 1, wherein the organic solvent B is an organic solvent that does not contain water.

7. The method for producing the organic solvent B according to claim 6, wherein the organic solvent B is a lower alcohol such as methanol or ethanol.

8. The method for producing the organic solvent B in which the organic compound is dissolved, supplied to the osmotic pressure-assisted reverse osmosis membrane, wherein a pressure less than the osmotic pressure of the organic solvent B in which the organic compound is dissolved is applied.

9. The method for manufacturing according to claim 1, wherein the osmotic pressure-assisted reverse osmosis membrane is a hollow fiber membrane.

10. The method for producing the organic compound according to claim 1, wherein the solubility of the organic compound in the organic solvent B is greater than the solubility of the organic compound in the solvent A.

11. The manufacturing method according to claim 1, wherein the separation membrane is an ultrafiltration membrane.

12. The manufacturing method according to claim 1, wherein the ultrafiltration membrane is a hollow fiber membrane.

13. The method for producing the product according to claim 1, wherein the organic compound is at least one selected from the group consisting of organic acids, aromatic compounds, fragrances, proteins, amine acids, vitamins, nucleic acids, and enzymes.

14. The method for producing the product according to claim 1, wherein solvent A is an aqueous or organic solvent, and organic solvent B is an organic solvent that does not contain water.

15. The organic solvent B is diluted with alcohol to a concentration of 20 to 50% by weight. The manufacturing method of claim 14, wherein the concentration is the concentration obtained when the weight of the organic solvent B and the alcohol are added together and the weight of the organic solvent B is used as the numerator.

16. The method for producing the method of claim 15, wherein the alcohol is a higher alcohol having 5 or more carbon atoms in its molecule.

17. An extraction system that dissolves the organic compound in the organic solvent B by continuously flowing a solvent A containing a specific organic compound through one space of a separation membrane and continuously flowing the organic solvent B through the other space of the separation membrane, thereby forming an interface between the solvent A and the organic solvent B via the separation membrane. A concentration system is provided in which the organic solvent B in which the organic compound has been dissolved in the extraction system is continuously supplied to an osmotic pressure-assisted reverse osmosis membrane, thereby obtaining the organic solvent B with a high concentration of the organic compound. An apparatus for producing the organic compound concentrated in the organic solvent B, comprising the above-mentioned organic solvent B.