Method and apparatus for producing organic compounds

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

[Technical Field]

[0001] This invention relates to a manufacturing method and apparatus for continuously concentrating, separating, and recovering useful organic compounds (organic acids, aromatic compounds, fragrances, etc.) with low energy consumption. [Background technology]

[0002] Methods for separating useful organic compounds dissolved in a solvent include extraction, distillation, and crystallization. For example, bioproducts produced by utilizing the functions of microorganisms, plants, and animals contain useful organic compounds in a very dilute state, and therefore require increased purity before use. However, because useful organic compounds exist dissolved in dilute solvents, conventional techniques present problems such as 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 sufficiently developed. In industry, for example, in petrochemical processes, the development of organic solvent reverse osmosis (OSRO) membranes is being considered for the separation of alcohols and aromatic compounds. In addition, organic solvent nanofiltration membranes (OSN) are used in organic solvent recycling processes in the food and pharmaceutical fields (see, for example, Patent Document 1), but there is a need to develop new separation membranes that possess the necessary properties for organic solvent separation, such as resistance to organic solvents, chemical resistance, and pressure resistance.

[0004] Non-patent document 1 discloses a continuous extraction process that uses a hollow fiber contactor in a microfiltration membrane to interact a culture medium and artificial green algae with a dodecane solvent phase to extract patchoulol produced by the algae, and then continuously extracts patchoulol from dodecane using methanol with a nanofiltration membrane, thereby enabling concentration of patchoulol in the methanol solvent phase and recovery of dodecane for reuse.

[0005] Furthermore, Non-Patent Document 2 discloses a method for extracting phenol from a liquid culture medium of Pichia yeast (P. pastoris into which the gene for the phenol production pathway has been introduced) using a hollow fiber membrane contactor to extract phenol into the organic solvent triphtyrin. Furthermore, 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. The OSRO membrane is an RO membrane specifically designed for use with organic solvents. In contrast, the osmotically assisted reverse osmosis (OARO) membrane is an RO membrane that reduces the osmotic pressure difference across the membrane by placing an osmotic medium on the secondary side and bringing it into contact with the liquid on the primary side via the membrane. This allows for a faster rate of solvent permeation through the membrane even with low pressure applied to the primary side. Furthermore, Non-Patent Document 4 discloses a hybrid membrane process combining osmotic-assisted reverse osmosis (OARO) and reverse osmosis (RO) to further facilitate the reuse of water and nutrients from wastewater flows.

[0006] However, conventional techniques can extract organic compounds from solvents containing water, but it is difficult to extract only organic substances from organic solvents. Furthermore, commercially available separation membranes cannot withstand high concentrations of organic solvents for extended periods, making continuous concentration, separation, and recovery extremely difficult. Therefore, there is a need for a method or 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 series of processes with lower energy (lower pressure) compared to conventional methods, without the need for distillation or crystallization. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] International Open Pamphlet WO2023 / 127611 [Non-patent literature]

[0008] [Non-Patent Document 1] S. Overmans et al., Continuous extraction and concentration of secreted metabolites from engineered microbes using membrane technology, Green Chemical, 24, 5479 (2024). [Non-Patent Document 2] 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. [Non-Patent Document 3] C. Liu et al., Organic solvent reverse osmosis membranes for organic liquid mixture separation: A review, 620 (2021) 118882. [Non-Patent Document 4] 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.

Summary of the Invention

Problems to be Solved by the Invention

[0009] The inventors have successfully extracted useful organic compounds from a stock solution containing organic compounds using a separation membrane, extracted the membrane at a lower energy (low pressure) compared to the conventional method from an organic solvent, and used the osmotic pressure-assisted reverse osmosis (OARO) method to concentrate and recover the useful organic compounds to a desired concentration.

[0010] An object of the present invention is to provide a production method for continuously concentrating, separating, and recovering useful organic compounds with low energy. Another object is to provide a production method and a production apparatus for concentrating, separating, and recovering a useful organic compound after membrane extraction of the useful organic compound from a solvent.

Means for Solving the Problems

[0011] To solve the above problems, the production method of the present invention provides the following [1]- 16 and the production apparatus of the present invention provides the following 17 . [1] The method comprises an extraction step in which a solvent A containing a specific organic compound is continuously flowed through one side of a separation membrane, and an organic solvent B is continuously flowed through the other side of the separation membrane, thereby forming an interface between solvent A and organic solvent B via the separation membrane and dissolving the organic compound in organic solvent B; and a concentration step in which the organic solvent B containing the dissolved organic compound from the extraction step is continuously supplied to an osmotic pressure-assisted reverse osmosis membrane, thereby obtaining organic solvent B with a high concentration of the organic compound. Production method. [2] The membrane module comprises a first chamber in which organic solvent B is continuously supplied during the concentration process and the organic solvent B with a high concentration of organic compounds is discharged, and a second chamber located next to the first chamber via an osmotic-assisted reverse osmosis membrane, into which organic solvent B with a lower concentration of organic compounds moves through the osmotic-assisted reverse osmosis membrane and is discharged. The production method according to claim 1. [3] The organic solvent B discharged from the second chamber is supplied to the other space of the separation membrane. , the production method described above 2 . [4] A portion of organic solvent B, which has a high concentration of organic compounds discharged from the first chamber, is supplied to the second chamber. , the above 2 or [3] The production method described in.​ [5] The membrane modules are formed in multiple layers. and the manufacturing method described in the above 2 to . [6] Organic solvent B is an organic solvent that does not contain water. and the manufacturing method described in the above 1 . In this specification, "water-free organic solvent" refers to an organic solvent that does not contain water. However, commercially available organic solvents may contain some water depending on their purity, and it is also possible that organic solvents used in actual plant operation may contain moisture from the air. Therefore, it does not mean an organic solvent that contains absolutely no water; it is permissible for it to contain 1% or less water. [7] Organic solvent B is a lower alcohol such as methanol or ethanol. and the manufacturing method described in the above 6 . [8] In an osmotic-assisted reverse osmosis membrane, the organic solvent B in which the organic compound is dissolved is subjected to a pressure less than the osmotic pressure of the organic solvent B in which the organic compound is dissolved. and the manufacturing method described in the above 1 . [9] Osmotic-assisted reverse osmosis membranes are hollow fiber membranes. and the manufacturing method described in the above 1 .

[10] The solubility of an organic compound in organic solvent B is greater than the solubility of an organic compound in solvent A. and the manufacturing method described in the above 1 .

[11] The separation membrane is an ultrafiltration membrane. and the manufacturing method described in the above [1] to .

[12] The ultrafiltration membrane is a hollow fiber membrane, according to the manufacturing method described in [1] above. .

[13] The method of production described in [1] above, wherein the organic compound is selected from at least one of the group consisting of organic acids, aromatic compounds, fragrances, proteins, amine acids, vitamins, nucleic acids, and enzymes. .

[14] Solvent A is an aqueous or organic solvent, and organic solvent B is an organic solvent that does not contain water. , As described in [1] above manufacturing method

[15] Organic solvent B is diluted with alcohol to a concentration of 20-50% by weight. The concentration is calculated by using the weight of organic solvent B as the numerator and the combined weight of organic solvent B and alcohol as the denominator. and the manufacturing method described in the above

[14] .

[16] a The manufacturing method described in the above

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

[17] An apparatus for producing an organic compound concentrated in an organic solvent B, comprising: an extraction system that continuously flows solvent A containing a specific organic compound through one space of a separation membrane and organic solvent B through the other space of the separation membrane to form an interface between solvent A and organic solvent B, thereby dissolving the organic compound in organic solvent B; and a concentration system that continuously supplies organic solvent B containing the organic compound from the extraction system to an osmotic pressure-assisted reverse osmosis membrane, thereby obtaining organic solvent B with a high concentration of the organic compound.

Advantages of the Invention

[0012] According to the present invention, there is an effect that useful organic compounds can be continuously concentrated, separated, and recovered with low energy

Brief Description of the Drawings

[0013] [Figure 1] Schematic diagram of the manufacturing method by membrane extraction - membrane concentration [Figure 2] Configuration diagram of the hollow fiber membrane module [Figure 3] Concentration configuration diagram by the osmotic pressure - assisted reverse osmosis (OARO) method of the partial reflux type​ [Figure 4] experimental system for membrane extraction [Figure 5] Concentration experimental system using OARO membrane 1 [Figure 6] Experimental results of concentration using OARO membrane 1 [Figure 7] Experimental system and results of enrichment using OARO membrane 2 [Figure 8] A graph showing the vapor pressure measurement results and osmotic pressure of benzoic acid (in MeOH solution). [Figure 9] Diagram illustrating the comparison between batch processing and continuous processing in the extraction process. [Figure 10] Graph showing the decrease in malic acid concentration over time in the aqueous phase. [Figure 11] Graph showing the correlation between tri-n-octylamine (TOA) concentration and partition coefficient. [Modes for carrying out the invention]

[0014] Hereinafter, an example of an embodiment of the present invention will be described in detail with reference to the drawings. It should be noted that the scope of the present invention is not limited to the following embodiments or illustrated examples, and numerous modifications and variations are possible.

[0015] (1) Regarding organic compounds In this invention, organic compounds include organic acids, aromatic compounds, fragrances, and the like. Here, organic acids are a general term for organic compounds that exhibit acidity, such as carboxylic acids having a carboxyl group and sulfonic acids having a sulfo group. Specifically, 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 are used as seasonings in many processed foods and are also used as useful substances expected to have disinfecting, antibacterial, deodorizing, and antifungal properties. Aromatic compounds are a general term for organic compounds that mainly contain a benzene ring, such as toluene, phenol, benzoic acid, xylene, cresol, phthalic acid, biphenyl, benzophenone, triphenylmethane, and naphthalene. Fragrances are compounds that have an aroma, and refer to organic compounds or mixtures used to give fragrance to foods and cosmetics, such as aliphatic higher hydrocarbons, terpene hydrocarbons, aliphatic higher alcohols, aliphatic higher aldehydes, ethers, esters, and ketones. In the present invention, solvent A is an aqueous phase or an organic phase and contains the above-mentioned useful organic compounds.

[0016] (2) Regarding organic solvents (2-1) When solvent A is in the aqueous phase In the present invention, the organic solvent must be an organic solvent that is substantially insoluble in water at room temperature when solvent A is the aqueous phase. Specifically, examples include glycerol triesters to which carboxylic acids having 3 to 12 carbon atoms are bonded, phosphate esters to which alcohols having 3 to 12 carbon atoms are bonded, and dodecane, a linear alkane having 12 carbon atoms. As glycerol triesters, lauric acid, undecenoic acid (12 carbon atoms), capric acid (10 carbon atoms), caprylic acid (8 carbon atoms), triplyline (glycerol tripylate), and trippropionine (glycerol tripionate) can be preferably used in combination with glycerol. 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 that the solvent is substantially insoluble in water at room temperature is not required; any organic solvent that does not mix with the organic phase of solvent A via a separation membrane such as an ultrafiltration membrane can be used. For example, C1 and C2 alcohols (methanol, ethanol, etc.) can be used as organic solvents.

[0018] In the manufacturing method of the present invention, in the extraction step performed as a pretreatment before the concentration step, organic compounds that dissolve 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 ultrafiltration membrane will be described below. (3) Regarding ultrafiltration membranes Ultrafiltration membranes have a pore size of 5-100 nm or a nominal molecular weight cutoff of 5-1,000 kD, which is larger than reverse osmosis membranes (RO membranes, NF membranes) but smaller than microfiltration membranes (MF membranes), and are referred to as UF (Ultrafiltration membrane) membranes. The material of the ultrafiltration membrane in the present invention can be, for example, cellulose, cellulose ester, aromatic polyamide, polyvinyl alcohol, polyethersulfone, polysulfone, polyvinylidene fluoride, polyacrylonitrile, ceramic, polycarbonate, sulfonated polyethersulfone, etc. For ease of handling, the material of the ultrafiltration membrane is preferably an organic material. As hydrophilic organic materials, polysulfone and polyethersulfone are preferred. Furthermore, while various membrane shapes such as flat membranes and hollow fiber membranes can be used, a hollow fiber membrane is 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 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. This physically stabilizes the interface and forms such a separation interface across the entire surface of the membrane, significantly increasing the surface area of ​​the interface and dramatically increasing the rate at which useful organic compounds move from solvent A to the organic solvent through the ultrafiltration membrane.

[0020] The ultrafiltration membranes that can be used in this invention are all that are capable of separating useful organic compounds from solvent A, regardless of their physical shape or chemical composition. For example, it is necessary for a useful organic compound present in solvent A to move into an organic solvent via an ultrafiltration membrane, and therefore the membrane must have pores. The size and number of pores can be appropriately selected depending on the type of solvent used and the type of useful organic compound.

[0021] The hollow fiber ultrafiltration membrane in this invention (hereinafter sometimes simply referred to as the hollow fiber membrane) may be surface-treated to prevent deterioration during use. In contact between the hollow fiber membrane and an organic solvent, there is a possibility that the organic solvent may penetrate into the material constituting the hollow fiber membrane, causing it to swell, or that the hollow fiber membrane may partially dissolve. As a result, the strength of the hollow fiber membrane may decrease, making it difficult to use it continuously for a long period of time. Alternatively, the organic solvent may leak into solvent A. As a method to improve the surface properties of such a hollow fiber membrane, it is preferable to hydrophilize the surface of the ultrafiltration membrane. Hydrophilization treatment improves the resistance of the hollow fiber membrane to organic solvents and prevents the organic solvent from passing through the membrane and leaking out.

[0022] One method for hydrophilizing the interface between a hollow fiber membrane and an organic solvent is to blend various hydrophilic materials together with the membrane-forming material when manufacturing the hollow fiber membrane. Preferred hydrophilic materials for this purpose include hydrophilic polymers such as polyvinylpyrrolidone and hydrophilic inorganic materials such as colloidal silica. Alternatively, it is possible to expose the hydrophilic material on the membrane surface by coating after the hollow fiber membrane has been formed. If the material used to form the hollow fiber membrane is a polymer material, it is also possible to manufacture copolymers using various known methods and use them. In this case, suitable hydrophilic materials include vinylpyrrolidone, acrylic acid, 2-hydroxyethyl acrylate, acrylamide and its derivatives, vinyl acetate, and other hydrophilic monomers, or random copolymers, block copolymers, graft copolymers, etc., formed using copolymer monomers that are hydrophilized by hydrolysis or the like.

[0023] Other hydrophilization treatments that are preferably used include various plasma treatments. In this case, low-temperature plasma treatment methods are preferred, and a method in which plasma generated between electrodes under atmospheric pressure and high voltage is brought into contact with the film surface to perform hydrophilization is particularly preferred. However, it is also preferable to hydrophilize the film surface by using vacuum plasma or by low-temperature thermal spraying of various ceramics or metals.

[0024] As an example of the material constituting the hollow fiber membrane in the present invention, it is preferable to use a material that includes at least one selected from various polymers, ceramics, and metals, and has good water resistance and chemical resistance, as well as excellent mechanical strength, pressure resistance, and heat resistance. In particular, it is preferable to use an organic polymer-based material that is easy to mold and process. More specifically, it is preferable that the main component of the membrane material is 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 this invention is preferably a tubular or fibrous separation membrane with a hollow center, having a longitudinal length in the range of 50 to 2000 mm, and more preferably an average outer diameter in the range of 0.4 to 10 mm. The inner diameter of the hollow fiber membrane is preferably in the range of 0.3 to 9.5 mm. Furthermore, the substantial layer sandwiched between the outer surface and inner diameter of the hollow fiber membrane forms a porous structure having a porosity in the range of 5 to 90%, more preferably 30 to 90%, and the pore diameter on the outer surface where the porous structure is exposed on the outer surface of the hollow fiber membrane is preferably in the range of 5 to 100 nm, and the pore diameter on the inner surface exposed on the inner diameter surface is preferably in the range of 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 diameter on the outer surface may be smaller than the pore diameter on the inner surface, and the mesh structure forming the separation layer may be formed with a mesh density that slopes from dense to sparse or vice versa from the outer surface to the inner surface. Here, solvent A and the organic solvent can be placed either outside or inside the hollow fiber membrane. That is, by placing solvent A in the internal channel of the hollow fiber membrane and the organic solvent on the outer surface of the hollow fiber membrane, it is possible to efficiently extract useful organic compounds. Alternatively, the organic solvent can be placed in the internal channel of the hollow fiber membrane, allowing for the extraction and separation of 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 in the present invention has a substantial layer having pore diameter and porosity within the above-described range. However, it is preferable to optimize the pore diameter and porosity in order to prevent leakage of organic solvents into solvent A and to improve the extraction efficiency of useful organic compounds. For this purpose, the pore diameter and porosity of the substantial layer can be controlled by adding an additive to the material used when manufacturing the hollow fiber membrane. As the additive, various soluble pore-forming agents known as pore-forming agents can be used. For example, various inorganic salts such as table salt, various sugars such as sucrose, and polymer microparticles such as acrylic or styrene polymer microparticles, and silicone microparticles such as colloidal silica, which have their size and shape controlled in advance, can be used. Alternatively, when manufacturing hollow fiber membranes, it is possible to produce hollow fiber membranes with various pore sizes and porosities by using non-solvent-induced phase separation (NIPS) or thermal-induced phase separation (TIPS) methods, and by combining two or more incompatible polymers as materials to induce a phase separation structure, thereby selectively dissolving and removing one of the polymer components. A variety of incompatible and dissolvable polymers suitable for this purpose can be used.

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

[0028] As a separation process for useful organic compounds from solvent A using a hollow fiber membrane, it is possible to extract and separate the organic compound from solvent A into the organic solvent by dissolving the organic compound in an organic solvent that is immiscible with solvent A and separating solvent A and the organic solvent through the hollow fiber membrane. The organic solvent used must be substantially insoluble in solvent A at room temperature in order to prevent mixing and emulsification between solvent A and the organic solvent through the hollow fiber membrane. Solvent A and the organic solvent may be placed either outside or inside the hollow fiber membrane. In either case, the extraction efficiency of the organic compound can be increased by adjusting the flow velocity 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 in a form where both the supply side and the permeate side of the internal liquid are open, or in a form where one side of the permeate side is sealed by potting. The hollow fiber membrane can be used as an integrated separation device as 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 multiple hollow fiber membranes together, an organic solvent is introduced into the hollow fiber membrane, and solvent A is placed on the outside of the hollow fiber membrane inside the module.

[0029] In a preferred embodiment of the present invention, an organic solvent introduced into the hollow fiber is circulated by a pump, allowing solvent A and the organic solvent to continuously come into contact through the hollow fiber membrane, thereby enabling the separation of useful organic compounds. When solvent A is placed inside the hollow fiber membrane, the surface of the hollow fiber membrane may become clogged with various insoluble components generated in solvent A, hindering the diffusion of useful organic compounds. In contrast, a system in which the organic solvent is placed inside the hollow fiber membrane is preferable 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 using a pump or the like to more efficiently separate useful organic compounds.

[0030] (4) About Osmotic Reverse Osmosis (OARO) The OARO method is a separation membrane with a pore size of 2 nm or less, which is an application of the RO method. In the RO method, a feed solution is flowed through one side of the membrane, and water is permeated by applying a pressure higher than the osmotic pressure of the feed solution. On the other hand, the OARO method is a process in which two solutions with a small or similar osmotic pressure difference and salt concentration and osmotic pressure are flowed through the high-pressure side and low-pressure side of a semipermeable membrane, respectively, and a concentrated solution and a diluted solution are obtained by pressurizing one side. In the OARO method, the osmotic pressure difference between the two sides of the membrane can be minimized, so the operating pressure required for the feed solution to permeate the membrane can be greatly reduced. Similar to the RO method, the OARO method achieves membrane permeation by applying a pressure higher than the osmotic pressure difference between the two sides of the membrane.

[0031] The membranes that can be used in the OARO method are, like those in the RO method, of two types in terms of membrane shape: flat membranes and hollow fiber membranes. The membrane material is preferably a material containing at least one of cellulose resins, polysulfone resins, and polyamide resins. Cellulose resins are preferably cellulose acetate resins, more preferably cellulose acetate, and even more preferably cellulose triacetate from the viewpoint of durability. Polysulfone resins are preferably polyethersulfone resins, and more preferably sulfonated polyethersulfone.

[0032] Here, the membrane separation method of the OARO method will be explained with reference to Figure 3(1). In the OARO membrane separation method, the feed solution 36 (high-pressure side solution) is supplied to the first chamber 33a (high-pressure side) by applying a first pressure with a liquid transfer pump 35, and the reflux solution 38 (low-pressure side solution) is supplied to the second chamber 34a at a second pressure lower than the first pressure. This transfers the solvent contained in the feed solution in the first chamber 33a to the reflux solution in the second chamber 34a via the separation membrane 32a. As a result, the concentrated solution (concentrated feed solution) is discharged from the first chamber 33a, and the diluted solution (diluted reflux solution) is discharged from the second chamber 34a. This concentrates the feed solution and dilutes the reflux solution. In the above explanation, Figure 3(1) was used to illustrate the feed solution and reflux solution, but the same principles apply to separate solutions. Also, in Figure 3(1), the separation membrane 32a is depicted as a flat membrane for simplification, but hollow fiber membranes and flat membranes are assumed. In particular, hollow fiber membranes can increase the membrane surface area per unit volume of the membrane module, thereby increasing the membrane permeation flow rate per unit volume of the membrane module.

[0033] Furthermore, the OARO method allows for increasing the concentration to near saturation by using a multi-module configuration. Figure 3(1) shows a configuration of five OARO membrane modules, where a portion of the concentrated liquid 37 obtained from the supply liquid 36 through the five OARO membrane modules is refluxed to become reflux liquid 38, and finally discharged as diluent 39. In Figure 3(1), 40, 41, and 45 are pressure gauges, 46 is a flow meter, 42 is a back pressure valve, and 43 and 44 are flow control valves. Note that this shows a configuration of five OARO membrane modules, but this is just one example.

[0034] As shown in Figure 3(2), the concentration increases through each of the OARO membrane modules (32a to 32e) in the first to fifth series, and a refluxed solution 38, partially refluxed from the final concentrated solution 37, flows through the fifth series, fourth series, ..., and first series, and is discharged from the first series as a diluent 39. In each series of separation membranes (OARO membrane modules), the osmotic pressure difference between the two sides of the membrane can be minimized, and the operating pressure required for permeation through the membrane can be significantly reduced.

[0035] The present invention will be further described in detail by the following examples, but the present invention is not limited to these examples. Percentages in the examples are by mass unless otherwise specified. [Examples]

[0036] (Preparation of hollow fiber ultrafiltration membranes) N,N-dimethylacetamide (DMAC) was used as the solvent. 80 parts of DMAC were mixed with 18 parts of polyvinylidene fluoride (PVDF; Arkema® Kynar) and 2 parts of polyvinylpyrrolidone (PVP; K-30; manufactured by Fujifilm Wako Pure Chemical Industries). The mixture was left at room temperature overnight to obtain a uniformly dissolved solution. To prepare the hollow fiber membrane, a non-solvent-induced phase separation method (NIPS method) was used. The PVDF solution containing PVP was introduced to the outer circumference of a double-tube nozzle, while simultaneously introducing deionized water as the coagulation solution into the central discharge port of the double-tube nozzle. The PVDF solution and coagulation solution (deionized water) were simultaneously discharged from the double-tube nozzle into a coagulation bath filled with water adjusted to 40°C. The resulting hollow fiber membrane, consisting of a precipitated PVDF / PVP blend, was wound up, lifted from the coagulation bath using a roller, and wound 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 two days, then immersed in a 50% glycerin aqueous solution at room temperature for three days to remove soluble components from the membrane. After that, the glycerin was 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 actual film thickness of 0.1 mm.

[0038] The average thickness of the substantial layer of the hollow fiber membrane is 0.2 mm, and the interior of the substantial layer forms a network structure with pores averaging around 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 network structure inside the substantial layer, and further connect to voids formed on the inner surface of the hollow fiber membrane, thus communicating with the porous membrane on the inner surface. The porosity of the substantial layer, calculated from the ratio of mass to volume of the substantial layer, was found to be approximately 87%.

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

[0040] (Fabrication of hollow fiber membrane modules) Using the hollow fiber membrane prepared in Example 1, it was cut to a length of 30 cm, and 10 to 30 strands were bundled together and fixed inside a tube with an isocyanate adhesive, leaving both ends open. The tube was provided with two openings perpendicular to the longitudinal direction of the hollow fiber membrane, creating a structure that allows solvent A to circulate. Figure 2 shows the configuration 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 other externally connected tubes and connectors (21a, 21b), and organic solvents (18a, 18b) in externally provided containers circulate inside the hollow fiber membranes. An inlet opening (22a) and an outlet opening (22b) are provided outside the hollow fiber membranes within the hollow fiber membrane module (20) to allow the circulation of solvent A (11). Useful organic compounds (12) enter the organic solvent inside the hollow fiber membranes from solvent A (11) outside the hollow fiber membranes within the hollow fiber membrane module (10). The fabricated hollow fiber membrane module had a volume fraction occupied by the hollow fiber membrane of 44%, and the surface area of ​​the hollow fiber membrane was 213 cm². 3 That was the case.

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

[0043] (1) OARO membrane module 1 (manufactured by Toyobo MC Corporation, Holosep Mini® registered trademark; for details, please refer to the URL https: / / www.toyobo-mc.jp / products / hollosep_mini / ) (1-1) Bilateral fluid delivery system 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, after about 1 hour from 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 internal pressure was maintained, and the intermembrane differential pressure (the difference between the external and internal pressures of the membrane module) was 1.5 MPa. In other words, at the start, there was an intermembrane differential pressure (driving force) of about 5 MPa, but after about 1 hour, the intermembrane differential pressure decreased to about 1.5 MPa (5-3.5). However, as shown in Figure 6(1-1), the concentration of benzoic acid increased from 20 wt% at the start to 21.7 wt% at the outer outlet after 20 hours, while the concentration at the inner outlet was diluted to 18.0 wt%. This indicates that 20 wt% benzoic acid (in MeOH solution) could be concentrated by the OARO method at a membrane differential pressure of 1.5 MPa.

[0044] (1-2) Partial recirculation system 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 dilution side was at approximately atmospheric pressure, and there was a differential pressure (driving force) of about 5 MPa between the membranes. However, similar to the double-sided fluid delivery method, the differential pressure between the membranes decreased to about 1.5 MPa after about 1 to 2 hours. As a result, as shown in Figure 6(1-2), the concentration of benzoic acid increased from 20 wt% at the start to 22.2 wt% in the concentrated solution and diluted to 18.4 wt% in the diluted solution after 18 hours. 20 wt% benzoic acid (in MeOH solution) could be concentrated using the OARO method with partial reflux at a membrane differential pressure of 1.5 MPa. To concentrate benzoic acid (in MeOH solution) using OARO membrane module 1, we pressurized it to 5 MPa, but the pressure on the low-pressure side rose rapidly, and we were only able to secure an effective intermembrane pressure difference of 1.5 MPa. Nevertheless, 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, please refer to 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 injected at a flow rate of 2 mL / min without pressure, with a volume of 200 mL, into a flat membrane (membrane area 7.55 cm²). 2 The solution was supplied to the upper side (nonwoven fabric side) of the flat membrane, and 200 mL of 20 wt% benzoic acid (in MeOH solution) was supplied 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 (circulating liquid delivery system on both sides). Then, only the lower side was pressurized and concentration was performed using the OARO method (the intermembrane pressure difference is the difference between the lower and upper pressures). As a result, as shown in Figure 7(2), concentration using the bilateral OARO method increased the concentration of benzoic acid from 20 wt% at the start to 24.9 wt% in the concentrate and diluted to 17.3 wt% in the dilution after 23 hours. In concentration using the OARO method with the flat membrane of OARO membrane module 2, it was confirmed that 20 wt% benzoic acid (in MeOH solution) could be concentrated to 25 wt%. Further higher concentrations are 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). For solutions with different concentrations of benzoic acid, vapor pressure measurements were taken, and the osmotic pressure was estimated from these measurements. The osmotic pressure of 20 wt% (1.47 mol / L) benzoic acid was approximately 3.5 MPa (35 bar). This means that in the OARO method using OARO membrane module 2, a solution with an osmotic pressure of 3.5 MPa could be concentrated at a membrane differential pressure of 3 MPa or less. In principle, it is impossible to concentrate a solution with an osmotic pressure of 3.5 MPa at a membrane differential pressure smaller than that using the RO method.

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

[0048] As shown in Figure 9, in batch processing, the concentration of the extraction solution increases over time, causing the difference in chemical potential to decrease over time and thus reducing the extraction capacity. In contrast, in continuous processing, as in the extraction process of this embodiment, the concentration of the extraction solution is kept constant, so the difference in chemical potential remains constant, and the extraction capacity is maintained.

[0049] (concentration process) 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 organic compounds (e.g., benzoic acid) extracted into the organic solvent 17 (e.g., MeOH) is supplied to the first chamber 33 (high-pressure side) by a liquid transfer pump 35 at a slightly higher pressure (first pressure), and a reflux solution 38, partially refluxed from the outlet, is supplied to 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. As a result, the concentrated solution 37 is discharged from the first chamber 33 and the diluted solution 39 is discharged from the second chamber 34. The diluent 39 flows to the extract side (organic solvent 17) of the extraction system (10) (arrow B), circulating between the extraction system and the concentration system. This enables a continuous purification (manufacturing) process using membrane extraction and membrane concentration.

[0050] (Experimental results of membrane extraction) Referring to Figure 4, the experimental results of membrane extraction of benzoic acid as an organic compound are explained. First, an aqueous solution of benzoic acid (initial concentration 0.25 wt%) was extracted using dodecane with a hollow fiber ultrafiltration membrane (hereinafter referred to as the hollow fiber membrane module). After extraction, the concentration of dodecane was 0.0116 wt%, and 0.133 wt% benzoic acid (in methanol solution) was extracted from the benzoic acid (in dodecane) using methanol as the organic solvent. Furthermore, if the organic compound is an organic acid, ketone-based organic solvents or hexane can be preferably used as the organic solvent for extraction. [Examples]

[0051] This example will focus on the extraction process. The extraction system (10) shown in Figure 1 includes a hollow fiber membrane module (20), an organic solvent (17) circulating inside the hollow fiber ultrafiltration membrane within the module, and 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 the CA membrane module) was used as the hollow fiber membrane module (20), and an aqueous malic acid aqueous solution was used as solvent A, and tri-n-octylamine (TOA) was used as the organic solvent (17) to perform membrane extraction of malic acid. A non-solvent-induced phase separation method was used to form the hollow fiber membrane. Here, cellulose diacetate is 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 tributyline, are also effective as organic solvents for extraction (17). Membrane extraction experiments were conducted by varying the TOA ratio in the extraction solution, and the extraction efficiency under each experimental condition was determined by the partition coefficient (D) and the overall mass transfer coefficient (K). a The evaluation was performed using [m / s].

[0052] Using a CA membrane module, an aqueous solution of 1 wt% malic acid was contacted with a 1-octanol solution of TOA, and the results of membrane extraction of malic acid in the aqueous solution (aqueous phase) are shown in Fig. 10. Fig. 10 is a graph showing the concentration decrease curve of the malic acid concentration in the aqueous phase with respect to time (a solution with a TOA to 1-octanol ratio of 3:7, i.e., a TOA concentration of 30 wt%). In addition, as the higher alcohol for diluting TOA, in addition to 1-octanol, higher alcohols with 5 or more carbon atoms in the molecule such as 1-pentanol, 1-hexanol, 1-decanol, 1-dodecanol, and oleyl alcohol are effective. As shown in Fig. 10, due to the contact between the aqueous solution and the extraction solution through the CA membrane module, the malic acid concentration in the aqueous solution decreased with time. It was found that the concentration reached equilibrium at around 50 hours. The overall mass transfer coefficient K a was calculated using the following formula from the concentration decrease curve of the malic acid concentration in the aqueous phase with respect to time, and K a = 1.77×10 -6 [m / s].

[0053]

Equation

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

[0055] The partition coefficient of malic acid was determined by measuring the malic acid concentration in the aqueous phase when equilibrium was reached after more than 50 hours of membrane extraction. Mixing of the extracted phase liquid into the aqueous phase could not be confirmed visually until the end of the extraction experiment. The dependence of the partition coefficient and overall mass transfer coefficient on the TOA concentration is shown in the correlation graph between TOA concentration and partition coefficient in Figure 11. The partition coefficient reached a maximum value when the TOA concentration was 30 wt%. Furthermore, it was found that the partition coefficient was generally above 50 when the TOA concentration was between 20 and 50 wt%. The overall mass transfer coefficient K a It did not depend significantly on the TOA concentration. These evaluation results showed that when the ratio of TOA to 1-octanol is in the range of 1:4 to 1:1, and particularly preferably 3:7, extraction using the CA membrane module proceeds efficiently without mixing of the extracted phase liquid with the aqueous phase.

[0056] Here, we will explain the method for fabricating CA membrane modules. 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. Then, the dissolved solution is pushed out through a double-pipe nozzle using a gear pump, and guided to a coagulation bath where it is coagulated to produce a hollow fiber membrane. Water is used for both the internal liquid and the coagulation solution. After the wound hollow fiber membrane is washed, any adhering water is replaced with a 50% aqueous glycerin solution, and it is dried at room temperature. The fabricated hollow fiber membrane is cut to an appropriate length, both ends are sealed with epoxy resin, and it is housed in a cylindrical shroud made of plastic to produce an external CA membrane module. An external membrane module is a device in which a membrane module is installed outside the reaction vessel, and a solute is moved between a solvent circulating inside the membrane and a solvent circulating outside the membrane while pressurized by a pump. In this embodiment, a CA membrane was used as the hollow fiber membrane module, but other membranes such as SPES (sulfonated polyethersulfone) membranes can also be used. However, PP (polypropylene) and Teflon® membranes, which are commonly used for membrane separation applications, are unsuitable because the organic phase leaks into the aqueous phase. [Industrial applicability]

[0057] This technology can be widely used for the purification of useful organic compounds dissolved in aqueous systems produced in bio-manufacturing processes such as bioprocesses involving microorganisms and bioreactors utilizing enzymes, as well as for the purification and concentration of organic compounds such as organic acids, aromatic compounds, and fragrances produced by conventional chemical synthesis. [Explanation of Symbols]

[0058] 1 Manufacturing equipment 10 Extraction strains 11 Solvent A 12 Organic compounds 17,18a,18b Organic solvents 13,18 Stirrer 15, 19, 35 Liquid transfer pumps 20 Hollow fiber membrane (ultrafiltration membrane) module 21a, 21b connectors 22a Entrance side opening 22b Outlet side opening 30 Concentrated line 32,32a~32e Separation membrane (OARO membrane module) 36 Extract 37 Concentrate 38 Reflux 39 Diluted solution 40, 41, 45 Pressure gauges 46 Flow meter 42 Back pressure valve 43,44 Flow control valve

Claims

1. An extraction step in which a solvent A containing a specific organic compound is continuously flowed through one space of a separation membrane, and a water-free organic solvent B is continuously flowed through the other space of the separation membrane, thereby forming an interface between solvent A and organic solvent B via the separation membrane and dissolving the organic compound in 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. Equipped with, In the aforementioned concentration step, the diluted solution is discharged. By returning the discharged dilution to the other space of the separation membrane, the organic compound concentrated in the organic solvent B by the extraction step and the concentration step is continuously purified. A method for producing the organic compound concentrated in the 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 according to claim 2 or 3, wherein a portion of the organic solvent B, whose concentration of the organic compound discharged from the first chamber has increased, is supplied into 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 method according to claim 1, wherein the organic solvent B is a lower alcohol having two or fewer carbon atoms, such as methanol or ethanol.

7. The method for producing the product according to claim 1, wherein the organic solvent B in which the organic compound is dissolved, supplied to the osmotic pressure-assisted reverse osmosis membrane, is subjected to a pressure less than the osmotic pressure of the organic solvent B in which the organic compound is dissolved.

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

9. The manufacturing method 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.

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

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

12. 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.

13. The method for producing the method according to claim 1, wherein the solvent A is an aqueous or organic solvent.

14. The organic solvent B is diluted to a concentration of 20 to 50% by weight with an alcohol not contained in the organic solvent B. The manufacturing method of claim 13, 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.

15. The method for producing the method according to claim 14, wherein the alcohol is a higher alcohol having 5 or more carbon atoms in its molecule.

16. An extraction system is provided in which a solvent A containing a specific organic compound is continuously flowed through one side of a separation membrane, and a water-free organic solvent B is continuously flowed through the other side of the separation membrane, thereby forming an interface between solvent A and organic solvent B via the separation membrane and dissolving the organic compound in organic solvent B. 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. Equipped with, In the aforementioned concentration system, the diluted solution is discharged. By returning the discharged dilution to the other space of the separation membrane, the organic compound concentrated in the organic solvent B by the extraction system and the concentration system is continuously purified. A apparatus for producing the organic compound concentrated in the organic solvent B.

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