WO2021193565A1 - Production method for cyclic compound or derivative thereof - Google Patents

Production method for cyclic compound or derivative thereof Download PDF

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Publication number
WO2021193565A1
WO2021193565A1 PCT/JP2021/011787 JP2021011787W WO2021193565A1 WO 2021193565 A1 WO2021193565 A1 WO 2021193565A1 JP 2021011787 W JP2021011787 W JP 2021011787W WO 2021193565 A1 WO2021193565 A1 WO 2021193565A1
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Prior art keywords
cyclic compound
solution
derivative
treatment
raw material
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PCT/JP2021/011787
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French (fr)
Japanese (ja)
Inventor
賢也 橘
藤原　大輔
隆一 村田
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住友ベークライト株式会社
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Priority to JP2022510501A priority Critical patent/JPWO2021193565A1/ja
Publication of WO2021193565A1 publication Critical patent/WO2021193565A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D9/00—Crystallisation
    • B01D9/02—Crystallisation from solutions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C62/30—Unsaturated compounds
    • C07C62/32—Unsaturated compounds containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
    • C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring

Definitions

  • the present invention relates to a method for producing a cyclic compound or a derivative thereof.
  • Patent Document 1 discloses a method of producing methane from biomass by microbial fermentation, then producing benzene from methane by a catalytic reaction, and further producing a benzene derivative from this benzene. Since the benzene derivative produced in this manner is used as a raw material for an aromatic polymer, it is possible to realize a polymer that does not depend on fossil resources.
  • the conventional method does not yet have sufficient efficiency in producing benzene derivatives. Specifically, when producing a benzene derivative such as phthalic acid from biomass via methane and benzene, there is a problem that the amount of benzene derivative synthesized is small for the labor and energy input.
  • Patent Document 1 discloses that benzene is purified by a distillation method or the like, and although it is possible to increase the purity of the benzene derivative by this, a large amount of energy is still consumed in that case.
  • An object of the present invention is to provide a production method capable of producing a high-purity cyclic compound or a derivative thereof in a high yield.
  • It has a crystallization step of precipitating the cyclic compound or its derivative from the raw material liquid by a crystallization treatment for controlling the temperature of the raw material liquid containing the cyclic compound or its derivative and a solvent.
  • the crystallization treatment is a treatment for controlling the temperature of the raw material liquid so that the concentration of the cyclic compound or its derivative in the raw material liquid is located in the semi-stable region. Derivative manufacturing method.
  • a high-purity cyclic compound or a derivative thereof can be produced in a high yield.
  • FIG. 1 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to the first embodiment of the present invention.
  • FIG. 2 is a graph showing an example of the relationship between the abundance ratio of a cyclic compound in a solution, the abundance ratio of ions of a cyclic compound in a solution, and pH.
  • FIG. 3 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to a third embodiment of the present invention.
  • FIG. 4 is a diagram for explaining the crystallization treatment according to the third embodiment of the present invention, in which the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract.
  • FIG. 5 is a diagram for explaining the crystallization treatment according to the comparative example, and when the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract, the relationship between them. It is a figure which shows.
  • FIG. 1 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to the first embodiment of the present invention.
  • the method for producing the cyclic compound or its derivative according to the present embodiment includes a raw material liquid preparation step S01, a first drying step S02, a redissolving step S03, an adsorption step S04, a second drying step S05, and an extraction step. It has S06, a precipitation step S07, and a solid-liquid separation step S08. According to such a method for producing a cyclic compound, a solid and high-purity cyclic compound or a derivative thereof can be produced in a high yield.
  • each step will be described in sequence.
  • the cyclic compound or its derivative is abbreviated as "cyclic compound”.
  • the method for producing a cyclic compound or a derivative thereof is omitted and is also referred to as a "method for producing a cyclic compound”. The cyclic compound will be described in detail later.
  • Biomass refers to organic resources derived from plants. Specific examples thereof include those that have been converted into starch, cellulose, or the like and stored, the body of an animal that grows by eating a plant, a product that can be processed from a plant or an animal, and the like.
  • cellulose-based crops pulp, kenaf, straw, rice straw, used paper, paper residue, etc.
  • wood, charcoal, compost natural rubber, cotton, sugar cane, okara, fats and oils (rapeseed oil, cottonseed oil, soybean oil, etc.) , coconut oil, castor oil, etc.
  • Carbohydrate crops corn, potatoes, wheat, rice, rice husks, rice bran, old rice, cassaba, sago palm, etc.
  • bagasse buckwheat, soybean, essential oil (pine root oil, orange oil, eucalyptus oil, etc.) Etc.), pulp black liquor, food waste, vegetable oil residue, marine product residue, livestock excrement, food waste, wastewater sludge, etc.
  • the biomass is pretreated to obtain a mixed sugar.
  • pretreatment include physical treatment, chemical treatment, physicochemical treatment, biological treatment, and the like, and one or a combination of two or more of these is adopted. ..
  • physical processing includes, for example, miniaturization processing by a disk mill, grinder, etc., compression processing, electromagnetic wave irradiation processing, electron beam irradiation processing, and the like.
  • the chemical treatment includes, for example, treatment with ionic liquids such as sulfuric acid, nitric acid, hydrochloric acid, phosphoric acid, and alkali, hydrothermal treatment, subcritical water treatment, supercritical fluid treatment, catalytic treatment, oxidant treatment, and heat.
  • ionic liquids such as sulfuric acid, nitric acid, hydrochloric acid, phosphoric acid, and alkali
  • hydrothermal treatment subcritical water treatment, supercritical fluid treatment, catalytic treatment, oxidant treatment, and heat.
  • Examples include a process of imparting energy and a process of imparting light energy.
  • examples of the physicochemical treatment include steam blasting treatment and ammonia blasting treatment.
  • the mixed sugar includes straw (rice straw, barley straw, wheat straw, rye straw, oat straw, etc.), non-edible agricultural waste such as bagasse, switchgrass, napier grass, and miscanthus.
  • Energy crops such as, wood chips, waste paper, etc. are saccharified with saccharifying enzymes, and saccharified liquids, or those containing molasses are also used.
  • Transformation treatment Next, the transformant is cultured or reacted in a reaction solution containing a mixed sugar to prepare a raw material liquid.
  • transformant is preferably cultured and grown in a medium prior to reaction with the mixed sugar.
  • the medium used includes a natural medium or a synthetic medium containing a carbon source, a nitrogen source, inorganic salts, other nutritional substances and the like.
  • the concentration of the nitrogen source in the medium varies depending on the nitrogen source used, but is, for example, 0.1 to 10 (w / v%).
  • the concentration of inorganic salts in the medium varies depending on the inorganic salts used, but is, for example, 0.01 to 1 (w / v%).
  • the concentration of the nutritional substance in the medium varies depending on the nutritional substance used, but is, for example, 0.1 to 10 (w / v%).
  • the pH of the medium is not particularly limited, but is preferably about 6 to 8.
  • reaction solution a natural reaction solution or a synthetic reaction solution containing a carbon source, a nitrogen source, inorganic salts and the like is used.
  • the concentration of the mixed sugar in the reaction solution is preferably 1 to 20 (w / v%), more preferably 2 to 10 (w / v%), and 2 to 5 (w / v%). Is more preferable.
  • the concentration of the total carbon source containing the mixed sugar is preferably 2 to 5 (w / v%).
  • the nitrogen source a nitrogen source appropriately selected from the above-mentioned nitrogen sources is used.
  • the concentration of the nitrogen source in the reaction solution varies depending on the concentration of the nutrient substance used, but is, for example, 0.01 to 1 (w / v%).
  • the inorganic salts those appropriately selected from the above-mentioned inorganic salts are used.
  • the concentration of the inorganic salts in the reaction solution varies depending on the concentration of the nutritional substance used, but is, for example, 0.1 to 10 (w / v%). Further, if necessary, those appropriately selected from the above-mentioned vitamins are used.
  • reaction temperature of the mixed sugar and the transformant that is, the survival temperature of the transformant is preferably 20 to 50 ° C, more preferably 25 to 47 ° C. Within this temperature range, cyclic compounds can be efficiently produced.
  • the reaction time is preferably 1 to 7 days, more preferably 1 to 3 days.
  • the culture may be a batch type, a fed-batch type, or a continuous type, but a batch type is particularly preferable.
  • the reaction may be carried out under aerobic conditions or under reducing conditions.
  • an aqueous solution for a reaction solution under reducing conditions can be obtained by removing the dissolved gas by heat treatment or decompression treatment.
  • the dissolved gas (particularly) is treated by treating with a reduced pressure of preferably 10 mmHg or less, more preferably 5 mmHg or less, still more preferably 3 mmHg or less for about 1 to 60 minutes, more preferably about 5 to 40 minutes.
  • Dissolved oxygen can be removed to prepare an aqueous solution for a reaction solution under reducing conditions.
  • an appropriate reducing agent for example, thioglycolic acid, ascorbic acid, cystine hydrochloride, mercaptoacetic acid, thiol acetic acid, glutathione, sodium sulfide, etc.
  • an appropriate reducing agent for example, thioglycolic acid, ascorbic acid, cystine hydrochloride, mercaptoacetic acid, thiol acetic acid, glutathione, sodium sulfide, etc.
  • these methods may be combined as appropriate.
  • the transformant After preparing the raw material liquid, the transformant is separated and removed.
  • the separation / removal method include a sedimentation separation method, a centrifugation method, a filtration separation method, and the like. Further, a method in which a plurality of these are combined may be used.
  • this step may be provided as needed, and may be replaced by, for example, a step of preparing a liquid containing a cyclic compound produced by recycling or the like.
  • the method for producing a cyclic compound or a derivative thereof according to the present embodiment includes a raw material liquid preparation step which is a step of preparing a raw material liquid from biomass as described above.
  • a raw material liquid preparation step which is a step of preparing a raw material liquid from biomass as described above.
  • the obtained raw material liquid may be concentrated if necessary.
  • concentration method examples include distillation, adsorption, extraction, membrane separation, dialysis, reverse osmosis, etc., and one or more of these are used in combination.
  • the raw material liquid is put into a stirring tank whose inner wall surface is a heat transfer surface, and the raw material liquid accumulated at the bottom is pumped up. Then, the raw material liquid is concentrated using a device that stirs the raw material liquid while spraying it on the inner wall surface.
  • the effective area of the heat transfer surface can be used to the maximum, and the concentration efficiency can be improved.
  • the generation of charring due to the drying of the heat transfer surface can be suppressed, and the coloring of the finally recovered solid can be suppressed.
  • the heating temperature in the concentration treatment is not particularly limited, but is preferably about 15 to 120 ° C, more preferably about 20 to 90 ° C. As a result, the efficiency of concentration can be improved while suppressing the generation of charring and the denaturation of solutes.
  • the raw material solution in the concentration treatment may be placed under reduced pressure. As a result, the volatilization of the solvent is promoted, and the concentration efficiency can be increased.
  • the pressure of the environment in which the raw material solution is placed is not particularly limited, but is preferably 80 kPa or less, and more preferably 0.1 to 50 kPa.
  • a salt of the cyclic compound may be prepared using a basic substance and dissolved in an aqueous medium. Further, the concentration treatment may be performed as needed and may be omitted.
  • the depressurization operation and the normal pressure return operation may be repeated as necessary.
  • the bubbles contract and expand, and the bubbles contained therein are promoted to rise and burst, so that the bubbles can be efficiently extinguished.
  • a decrease in concentration efficiency can be suppressed.
  • the time of the depressurization operation is not particularly limited, but is preferably about 1 to 10 seconds as an example. As a result, air bubbles can be efficiently removed.
  • First drying step S02 the raw material liquid is dried by a vacuum drying method to obtain a dried product (dry solid). Specifically, in the vacuum drying method, the raw material liquid is placed in a closed container and the inside of the closed container is depressurized. As a result, the difference in solvent partial pressure between the raw material liquid and the inside of the container is increased, and drying is promoted. As a result, the raw material liquid can be reliably dried in a short time to obtain a dried product. In addition, since small molecule impurity components can be efficiently removed, the purity and whiteness of the finally obtained cyclic compound can be increased.
  • the drying process by the vacuum drying method according to the present embodiment is a process of heating at a temperature of 65 to 125 ° C. at a pressure of 10 Pa or less.
  • heating under such conditions it is possible to more efficiently remove low-molecular-weight impurity components while suppressing the formation and coloring of the cyclic compound such as oxidation.
  • the purity and whiteness of the finally obtained cyclic compound can be increased.
  • the decrease of the cyclic compound can be suppressed, so that the yield of the finally obtained cyclic compound can be increased.
  • the pressure in the drying treatment is preferably 5.0 Pa or less, and more preferably 1.0 ⁇ 10 -6 Pa or more and 1.0 Pa or less in consideration of economic efficiency.
  • the temperature in the drying treatment is preferably 60 to 120 ° C, more preferably 90 to 110 ° C. This makes it possible to remove small molecule impurity components particularly efficiently without lowering the yield.
  • the cyclic compound may be denatured and the purity and yield may decrease.
  • the purity may decrease or the drying time may become long.
  • the heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 24 hours, and more preferably about 30 minutes to 6 hours.
  • a vacuum dryer equipped with the above-mentioned closed container and vacuum pump can be used.
  • the first drying step may be a step of obtaining an incompletely dried product.
  • the obtained dried product may be crushed or crushed as needed.
  • the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the redissolution step described later.
  • Redissolution step S03 Next, the obtained dried product is dissolved in a redissolving solvent to prepare a solution (resolving solution). By preparing the solution, the adsorption step described later becomes possible.
  • Adsorption step S04 the solution is subjected to an adsorption treatment, but prior to that, a treatment for ionizing the cyclic compound contained in the solution may be performed.
  • This treatment is a treatment for increasing the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be reduced.
  • the solution when preparing the solution (first solution) to be subjected to the adsorption treatment, the solution is prepared so that the abundance of the cyclic compound in the solution is smaller than the abundance of ions of the cyclic compound. As a result, in the subsequent adsorption treatment, it is possible to prevent the cyclic compound from being adsorbed on the adsorption medium and reduce the yield of the final cyclic compound.
  • the pH of the solution after the addition of the alkali is preferably about 5.0 to 7.5, and more preferably about 5.5 to 6.5. This makes it possible to reduce the abundance ratio of the cyclic compound in the solution. As a result, the probability that the cyclic compound is adsorbed on the adsorption medium can be reduced in the adsorption treatment described later.
  • the alkali include sodium hydroxide, potassium hydroxide and the like.
  • the adsorption treatment is a treatment in which the adsorption medium is brought into contact with the solution and the polymer components and the like in the solution are adsorbed on the adsorption medium.
  • impurities in the solution for example, organic components of the polymer are removed.
  • the purity of the finally obtained cyclic compound can be increased and coloring can be suppressed.
  • what is adsorbed and removed in the adsorption treatment is not limited to the organic component of the polymer, and any impurity may be used.
  • the temperature of the solution in the adsorption treatment is, for example, about 30 to 150 ° C.
  • the time of the adsorption treatment is not particularly limited, but is preferably about 10 minutes to 10 hours.
  • the amount of activated carbon added to 100 g of the solution is not particularly limited, but is preferably 0.01 to 3.0 g, more preferably 0.1 to 1.0 g. .. As a result, impurities can be adsorbed with a high probability, the purity of the final cyclic compound can be increased, and coloring can be suppressed.
  • this step may be performed as needed or may be omitted.
  • the redissolving step and the second drying step may be omitted in addition to the adsorption step.
  • the order of the adsorption steps is not limited to this embodiment, and may be, for example, before the first drying step or between the extraction step and the precipitation step.
  • the adsorption medium after the adsorption treatment is removed by a solid-liquid separation treatment such as filtration.
  • Second drying step S05 the solution that has undergone the adsorption step is dried to obtain a dried product, but prior to that, a treatment for deionizing the ions of the cyclic compound contained in the solution may be performed.
  • This treatment is a treatment for lowering the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be increased.
  • the solution when preparing the solution (second solution) to be subjected to the drying treatment, the solution is prepared so that the abundance of the cyclic compound in the solution that has undergone the adsorption step is smaller than the abundance of ions of the cyclic compound. Prepare. As a result, the yield of the cyclic compound can be increased in the extraction step after this step.
  • Examples of the treatment for lowering the ionization rate include a treatment for adding an acid.
  • the pH of the solution after the addition of the acid is preferably about 2.0 to 4.5, more preferably about 2.5 to 3.5. This makes it possible to increase the abundance ratio of the cyclic compound in the solution. As a result, the yield of the cyclic compound can be increased in the extraction step described later.
  • a concentration treatment may be performed separately from or in combination with the treatment for lowering the ionization rate. As a result, the time required for drying can be shortened and the required energy can be reduced. This concentration treatment can be performed under the conditions described above.
  • the solution that has undergone the adsorption step is dried.
  • the drying method in the second drying step include a boiling drying method, a spray drying method, a heat transfer drying method, an infrared drying method, a warm air drying method, and a vacuum drying method. Further, a plurality of types of drying methods including these drying methods may be applied in combination.
  • the same method as the first drying step described above, that is, the vacuum drying method may be used, but a different method may be used.
  • three typical drying methods other than the vacuum drying method will be sequentially described.
  • Boil-drying method In the boiling-drying method (boil-drying method), for example, a heating device such as a hot plate is used to heat the raw material liquid contained in the container. When the container is heated by heat conduction, the solvent in the raw material liquid evaporates. As the solvent evaporates, the solid dries and a dried product is obtained. According to such a boiling and drying method, since a simple device can be used, there is an advantage that the manufacturing cost can be easily reduced.
  • the heating temperature may be set above the temperature at which the solvent evaporates, so it differs depending on the type of solvent.
  • the temperature is preferably about 70 to 200 ° C, more preferably about 80 to 150 ° C.
  • the heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 10 hours, and more preferably about 30 minutes to 6 hours.
  • heating may be performed under a non-oxidizing gas, or heating may be performed while blowing a non-oxidizing gas, if necessary.
  • the obtained dried product may be crushed or crushed as needed.
  • the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the redissolution step described later.
  • Spray drying method is, for example, a method in which a raw material liquid is atomized by a nozzle in a drying chamber and brought into contact with warm air (spray drying). As a result, the solvent in the raw material liquid evaporates, and the precipitated solute is formed into particles. Therefore, a dried product that is easy to handle can be obtained.
  • the raw material liquid is atomized prior to drying, the specific surface area of the raw material liquid becomes large. Therefore, it is possible to raise the temperature uniformly in a short time, and it is possible to minimize the denaturation and decomposition of the solute.
  • the dried product has a high dissolution efficiency of the cyclic compound in the redissolution step described later.
  • the dried product obtained by the spray drying method has particles having a relatively uniform particle size. Therefore, the subsequent classification process can be omitted or simplified, and a dried product having high fluidity and easy handling can be obtained while suppressing the manufacturing cost.
  • the average particle size of the produced particulate dried product is not particularly limited, but is preferably about 5 to 300 ⁇ m, and more preferably about 10 to 200 ⁇ m. As a result, a dried product having high treatment efficiency in the steps described later and easy to handle from the viewpoint of fluidity and the like can be obtained.
  • the inlet temperature of the warm air is appropriately set according to the boiling point of the solvent, but as an example, it is preferably about 30 to 200 ° C, more preferably about 40 to 150 ° C.
  • the spray drying method since it can be dried in a closed space, it can be dried under an inert gas such as nitrogen or argon, if necessary. This makes it possible to suppress the oxidation of the dried product.
  • the heat transfer drying method is a method of indirectly heating the raw material liquid through, for example, a heat transfer surface. As a result, the solvent in the raw material liquid in contact with the heat transfer surface evaporates, and a dried product is obtained.
  • Examples of the heat transfer surface include metal bodies in the shape of discs, drums, cylinders, and the like.
  • the heat transfer drying method when the raw material liquid is sprayed on these heat transfer surfaces, it dries in a short time, and a dried product is obtained on the heat transfer surfaces. This dried product is scraped off with a scraper or the like and collected as a lump or a granular material.
  • the specific surface area of the raw material liquid becomes large. Therefore, it is possible to raise the temperature uniformly in a short time, and it is possible to minimize the denaturation and decomposition of the solute.
  • the temperature of the heat transfer surface is appropriately set according to the boiling point of the solvent, but is preferably about 70 to 200 ° C., more preferably about 80 to 150 ° C., for example.
  • the solvent can be efficiently evaporated while suppressing denaturation, decomposition, coloring and the like of the cyclic compound.
  • the heat transfer surface may be placed under reduced pressure. This makes it possible to increase the evaporation efficiency of the solvent and suppress oxidation and scorching of the cyclic compound.
  • the heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 10 hours, and more preferably about 30 minutes to 6 hours.
  • the obtained dried product may be crushed or crushed as needed. As a result, the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the extraction step described later.
  • the content of the solvent in the dried product is preferably 30% by mass or less, and more preferably 1% by mass or more and 20% by mass or less. As a result, the time and energy required for final drying can be reduced, so that efficient processing becomes possible.
  • Extraction step S06 the dried product is subjected to a solid-liquid extraction treatment with a solvent for solid-liquid extraction (extraction solvent) to obtain an extract.
  • the solid-liquid extraction process is a process for selectively extracting a cyclic compound contained in a dried product by utilizing its solubility in a solvent for solid-liquid extraction. That is, the cyclic compound can be selectively transferred to the solvent side where the cyclic compound is dissolved, and impurities such as inorganic salts can be left in the dried product. As a result, the purity of the cyclic compound contained in the extract can be increased.
  • Examples of the solvent for solid-liquid extraction include water, methanol, ethanol, isopropanol, acetone, acetonitrile, hexane, chloroform, tetrahydrofuran and the like.
  • the temperature of the solid-liquid extraction treatment is not particularly limited, but is preferably about 5 to 80 ° C, more preferably about 10 to 50 ° C.
  • the solubility of the solution can be optimized, so that the purity of the cyclic compound to be extracted and the extraction rate (extraction ability) can be compatible with each other.
  • the extraction rate may decrease.
  • the temperature exceeds the upper limit value, impurities are likely to migrate, and the purity of the cyclic compound may decrease.
  • the time of the solid-liquid extraction process is appropriately set according to the temperature, and is, for example, about 30 minutes to 10 hours.
  • the extraction rate can also be increased by heating under pressure.
  • the amount of the solvent for solid-liquid extraction is not particularly limited, but is preferably about 3 to 200 g per 1 g of the dried product, and more preferably about 10 to 50 g. This optimizes the amount of solvent. That is, if the amount of the solvent is less than the lower limit, the dissolution of the extract may be saturated and the extract may not be completely extracted. On the other hand, if the amount of the solvent exceeds the upper limit value, excess solvent may be generated and wasted. In addition, the amount of impurities extracted may increase, and the purity of the cyclic compound may decrease.
  • the solution after the adsorption step may be subjected to a liquid-liquid extraction treatment instead of the solid-liquid extraction treatment while omitting the second drying step.
  • the liquid-liquid extraction process is a process for selectively extracting a cyclic compound from a cyclic compound and other impurities contained in the solution by utilizing the difference in solubility in a solvent for liquid-liquid extraction. be.
  • the cyclic compound can be selectively transferred to the solvent side for liquid-liquid extraction. As a result, it becomes possible to take out a cyclic compound having a higher purity.
  • solvent for liquid-liquid extraction examples include n-butanol, isobutanol, iso-n-pentanol, isopentyl alcohol, n-hexanol, 2-hexanol, chloroform, hexane, diethyl ether, dichloromethane, carbon tetrachloride and the like. Can be mentioned.
  • Precipitation step S07 the extract is subjected to a precipitation treatment to precipitate the solute of the extract as a solid.
  • This precipitation treatment may be any treatment as long as the solvent in the extract can be removed. Specific examples of such a precipitation treatment include concentrated dryness, crystallization and the like.
  • concentrated dry solid is a process for extracting solutes by evaporating the solvent contained in the extract. According to such a treatment, the solid of the cyclic compound can be easily taken out from the extract by a simple operation such as heating or depressurizing. Moreover, since the solute can be taken out and dried at the same time, highly efficient processing becomes possible.
  • Examples of such a concentrated dry-solid treatment include a heating method, a decompression method, a gas spraying method, and the like, and one or a combination of these methods is used.
  • the method of heating the extract to volatilize the solvent is preferably used.
  • the heating temperature is not particularly limited as long as it is a temperature at which the solvent can be volatilized and is lower than the melting point of the cyclic compound, but is preferably about 50 to 300 ° C., preferably about 80 to 250 ° C. It is more preferable to have it. As a result, the solvent can be efficiently removed while suppressing the alteration of the cyclic compound.
  • Crystallization is a process of precipitating a solute by lowering the solubility of the solute in the extract. According to such a treatment, a highly pure cyclic compound can be taken out in a high yield.
  • the solvent is volatilized and removed from the extract by a treatment of changing the temperature of the extract and crystallization utilizing the temperature dependence of the solubility, heating or depressurization, and crystals.
  • the treatment of crystallization, the treatment of adding a solvent with low solubility of the solute and crystallization using the solvent type dependence of the solubility, the treatment of changing the pH of the extract and crystallization using the pH responsiveness of the solubility, etc. are mentioned, and one or more of these are used in combination.
  • the method of manipulating the temperature of the extract is preferably used. Since the temperature of the extract can be manipulated relatively easily, the method of manipulating the temperature of the extract is useful from the viewpoint of high workability.
  • the temperature range operated in the crystallization treatment varies depending on the composition of the cyclic compound, the type of solvent, and the like, and is not particularly limited, but is preferably about 5 to 80 ° C., for example, about 10 to 70 ° C. Is more preferable. This makes it possible to achieve both the purity and the yield of the cyclic compound to be taken out.
  • the crystallization treatment may be a batch treatment or a continuous treatment. Further, for the crystallization treatment, for example, a known stirring tank can be used.
  • the method of manipulating the temperature of the extract includes, in particular, an operation of lowering the temperature of the extract as a raw material liquid and an operation of stirring the extract, one operation at a time or an operation of repeating the operation a plurality of times. Is preferable. As a result, a high-purity cyclic compound can be finally recovered in a high yield.
  • the plurality of times is particularly preferably 3 times or more.
  • the amount of decrease in the operation of lowering the temperature is not particularly limited, and is appropriately selected according to the number of operations. As an example, it is preferably 1.0 ° C. or higher and 50 ° C. or lower, and more preferably 5.0 ° C. or higher and 30 ° C. or lower.
  • the rate of decrease in the operation of lowering the temperature is not particularly limited, but is preferably about 0.1 ° C./min or more and 5.0 ° C./min or less.
  • the cyclic compound can be efficiently precipitated while suppressing the entrainment of impurities, so that a high-purity cyclic compound can be finally obtained with high productivity.
  • the time for stirring the extract is not particularly limited, and is appropriately determined based on the precipitation rate of the cyclic compound. As an example, it is preferably about 3 hours or more and 72 hours or less, and more preferably about 10 hours or more and 48 hours or less.
  • the crystallization treatment preferably includes an operation of adding a seed crystal of a cyclic compound or a derivative thereof to be precipitated to the extract. By including such an operation, crystallization of the cyclic compound can be promoted. As a result, a higher purity cyclic compound can be precipitated.
  • the metastable region is a region between a solubility curve showing the temperature distribution of solubility and a persolubility curve showing the temperature distribution of persolubility in a Cartesian coordinate system with temperature and concentration as each axis.
  • the region where the concentration is higher than the metastable region is called the unstable region. If the temperature is changed by a route in which the concentration passes through the unstable region, the purity of the crystal may decrease. Therefore, the purity of the finally obtained cyclic compound may decrease.
  • Solid-liquid separation step S08 Next, the extract in which the cyclic compound is precipitated is subjected to a solid-liquid separation treatment.
  • the solid-liquid separation treatment examples include filtration separation, sedimentation separation, vacuum dehydration, pressure dehydration and the like, and filtration separation is particularly preferably used from the viewpoint of ease of operation and separation accuracy. Specifically, a centrifugal filter can be used. Further, the solid-liquid separation treatment may be a batch treatment or a continuous treatment.
  • the drying may be forced drying or natural drying.
  • the cyclic compound in the extract is separated and recovered.
  • the recovered cyclic compound may be subjected to other steps additionally provided.
  • Examples of other steps additionally provided include a series of steps of sequentially performing the same steps as the above-mentioned redissolving step and adsorption step, and then performing a reprecipitation step.
  • the reprecipitation step is a step of sequentially performing the same steps as the redissolution step and the same steps as the adsorption step, and then adding a poor solvent to the obtained solution.
  • a poor solvent By adding the poor solvent, precipitation of the cyclic compound can be obtained in the solution.
  • a cyclic compound having further increased purity By subjecting this precipitate to the same step as the solid-liquid separation step, a cyclic compound having further increased purity can be obtained.
  • the poor solvent is not particularly limited as long as it is miscible with water and has a lower solubility of the cyclic compound than water.
  • an arbitrary step other than the above may be added to this embodiment.
  • the method for producing a cyclic compound or a derivative thereof is a first drying step, which is a drying step of subjecting a raw material liquid containing the cyclic compound or a derivative thereof to a drying treatment to obtain a dried product. It also has an extraction step of extracting the cyclic compound or its derivative from the dried product into an extraction solvent to obtain an extract, and a precipitation step of precipitating the cyclic compound or its derivative from the extract.
  • the drying treatment is a treatment of heating the raw material liquid at a temperature of 65 to 125 ° C. at a pressure of 10 Pa or less. That is, such a drying treatment is a treatment by a vacuum drying method in which heating is performed in the above-mentioned temperature range.
  • the raw material liquid preparation step includes a concentration treatment for concentrating the raw material liquid, as described above.
  • concentration treatment for concentrating the raw material liquid, as described above.
  • the method for producing a cyclic compound or a derivative thereof according to the present embodiment includes a redissolving step and an adsorption step as described above.
  • the remelting step is a step provided between the first drying step and the extraction step, which are the drying steps, that is, after the first drying step and before the extraction step, and is a dried product. Is a step of preparing a re-dissolved solution by dissolving the above in a re-dissolving solvent.
  • the adsorption step is a step provided between the re-dissolution step and the extraction step, that is, after the re-dissolution step and before the extraction step, and is a step of applying the adsorption treatment to the re-dissolved solution.
  • the method for producing the cyclic compound or its derivative according to the present embodiment is the same as that of the first embodiment described above, that is, the raw material liquid preparation step S01, the first drying step S02, the remelting step S03, and the adsorption step S04. , A second drying step S05, an extraction step S06, a precipitation step S07, and a solid-liquid separation step S08.
  • the method for producing a cyclic compound of the present embodiment can also produce a solid, high-purity cyclic compound or a derivative thereof in a high yield.
  • each step will be described in sequence. Since the raw material liquid preparation step S01 is the same step as the raw material liquid preparation step S01 of the first embodiment described above, the description thereof will be omitted.
  • First drying step S02 The raw material liquid obtained in the raw material liquid preparation step S01 is dried to obtain a dried product (dry solid).
  • Examples of the method for drying the raw material liquid include the above-mentioned boiling drying method, spray drying method, heat transfer drying method, infrared drying method, warm air drying method, vacuum drying method and the like. Further, a plurality of types of drying methods including these drying methods may be applied in combination. Of the four typical drying methods, as for the boiling drying method, the spray drying method and the heat transfer drying method, each method described in the above-described first embodiment can be used.
  • the vacuum drying method as the drying method of the present embodiment will be described below.
  • Vacuum drying method In the vacuum drying method, the raw material liquid is placed in a closed container and the pressure inside the closed container is reduced. As a result, the difference in solvent partial pressure between the raw material liquid and the inside of the container is increased, and drying is promoted. As a result, the raw material liquid can be reliably dried in a short time to obtain a dried product. In addition, since small molecule impurity components can be efficiently removed, the purity and whiteness of the finally obtained cyclic compound can be increased.
  • the raw material liquid may be heated if necessary.
  • the heating temperature in that case is appropriately set according to the boiling point of the solvent, but as an example, it is preferably about 30 to 200 ° C., more preferably about 40 to 150 ° C., and about 60 to 120 ° C. It is even more preferable to have it.
  • the heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 24 hours, and more preferably about 30 minutes to 6 hours.
  • the pressure in the closed container in vacuum drying is not particularly limited as long as it is less than atmospheric pressure, but as an example, it is preferably 100 Pa or less, more preferably 20 Pa or less, and further preferably 10 Pa or less. As a result, it can be dried particularly efficiently, so that denaturation of the cyclic compound due to heating can be minimized. In addition, denaturation and coloring due to oxidation can be minimized.
  • the obtained dried product may be crushed or crushed as needed. As a result, the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the redissolution step described later.
  • the first drying step may be a step of obtaining an incompletely dried product.
  • the content of the solvent in the dried product is preferably 30% by mass or less, and more preferably 1% by mass or more and 20% by mass or less. As a result, the time and energy required for final drying can be reduced, so that efficient processing becomes possible.
  • the redissolving solvent a good solvent that dissolves the dried product is used.
  • the good solvent include water, methanol, hexane, chloroform and the like.
  • the valence of the cyclic compound is 0.
  • the ions of the cyclic compound are different depending on the type (chemical species) of the ions, but include, for example, monovalent ions, divalent ions and trivalent ions.
  • These valences are known to be pH dependent or temperature dependent. For example, when it has a pH dependence, it is possible to control whether the valence becomes 0 or 1, 2 or 3 by changing the pH of the extract. Become. Thereby, the abundance of the cyclic compound and the abundance of ions of the cyclic compound can be appropriately controlled in the solution.
  • FIG. 2 is a graph showing an example of the relationship between the abundance ratio of a cyclic compound in a solution, the abundance ratio of ions of a cyclic compound in a solution, and pH.
  • the abundance ratio of the cyclic compound having a valence of 0 gradually decreases, while the abundance ratio of the ion having a valence of 1 gradually increases.
  • the abundance ratio of the ion having a valence of 1 gradually decreases, while the abundance ratio of the ion having a valence of 2 gradually increases.
  • the abundance ratio of ions having a valence of 2 gradually decreases, while the abundance ratio of ions having a valence of 3 gradually increases.
  • the pH of the solution may be manipulated as an example. Thereby, the ionization rate of the cyclic compound in the solution can be controlled.
  • the pH of the solution after the addition of the alkali is preferably about 5.0 to 7.5, and more preferably about 5.5 to 6.5. This makes it possible to reduce the abundance ratio of the cyclic compound in the solution. As a result, the probability that the cyclic compound is adsorbed on the adsorption medium can be reduced in the adsorption treatment described later.
  • the alkali include sodium hydroxide, potassium hydroxide and the like.
  • Examples of the acid include formic acid, acetic acid, hydrochloric acid, propionic acid, butyric acid, valeric acid and the like.
  • the abundance of the cyclic compound in the solution (first solution) is smaller than the abundance of ions of the cyclic compound means that when the abundance of the former is 1, the abundance of the latter is , It means that the molar ratio to the former is less than 1. In this case, the abundance of the latter is preferably 0.9 or less, more preferably 0.8 or less, in terms of the molar ratio with respect to the former. This makes it possible to further reduce the probability that the cyclic compound will be adsorbed on the adsorption medium.
  • the adsorption treatment is a treatment in which the adsorption medium is brought into contact with the solution and the polymer components and the like in the solution are adsorbed on the adsorption medium.
  • impurities in the solution for example, organic components of the polymer are removed.
  • the purity of the finally obtained cyclic compound can be increased and coloring can be suppressed.
  • what is adsorbed and removed in the adsorption treatment is not limited to the organic component of the polymer, and any impurity may be used.
  • the adsorption medium is not particularly limited as long as it has an adsorptive ability, but is, for example, activated carbon, silica gel, zeolite, or the like. Then, in the adsorption treatment, any method is used as long as the adsorption medium can be brought into contact with the solution.
  • the amount of activated carbon added to 100 g of the solution is not particularly limited, but is preferably 0.01 to 3.0 g, more preferably 0.1 to 1.0 g. .. As a result, impurities can be adsorbed with a high probability, the purity of the final cyclic compound can be increased, and coloring can be suppressed.
  • the order of the adsorption steps is not limited to this embodiment, and may be, for example, before the first drying step or between the extraction step and the precipitation step. Further, the adsorption medium after the adsorption treatment is removed by a solid-liquid separation treatment such as filtration.
  • the abundance of the cyclic compound in the solution (second solution) that has undergone the adsorption step is such that the abundance of the cyclic compound is equal to or greater than the abundance of ions of the cyclic compound.
  • the yield of the cyclic compound can be increased in the extraction step after this step.
  • Examples of the treatment for lowering the ionization rate include a treatment for adding an acid.
  • the pH of the solution after the addition of the acid is preferably about 2.0 to 4.5, more preferably about 2.5 to 3.5. This makes it possible to increase the abundance ratio of the cyclic compound in the solution. As a result, the yield of the cyclic compound can be increased in the extraction step described later.
  • the difference between the pH of the solution (first solution) to be subjected to the adsorption treatment and the pH of the solution (second solution) that has undergone the adsorption step is preferably 1.5 or more and 5.0 or less, and 2.0 or more. It is more preferably 4.0 or less.
  • a concentration treatment may be performed separately from or in combination with the treatment for lowering the ionization rate. As a result, the time required for drying can be shortened and the required energy can be reduced. This concentration treatment can be performed under the conditions described above.
  • the solution (second solution) that has undergone the adsorption step is dried.
  • the second drying step may be performed in the same manner as the first drying step described above, but the method may be the same as or different from the first drying step.
  • Extraction step S06 in the same manner as in the first embodiment described above, the dried product is subjected to a solid-liquid extraction treatment with a solvent for solid-liquid extraction (extraction solvent) to obtain an extract.
  • Precipitation step S07 the extract is subjected to a precipitation treatment in the same manner as in the first embodiment described above, and the solute of the extract is precipitated as a solid.
  • Solid-liquid separation step S08 Next, in the same manner as in the first embodiment described above, the extract in which the cyclic compound is precipitated is subjected to a solid-liquid separation treatment.
  • the reprecipitation step is a step of sequentially performing the same steps as the redissolution step and the same steps as the adsorption step, and then adding a poor solvent to the obtained solution.
  • a poor solvent By adding the poor solvent, precipitation of the cyclic compound can be obtained in the solution.
  • a cyclic compound having further increased purity By subjecting this precipitate to the same step as the solid-liquid separation step, a cyclic compound having further increased purity can be obtained.
  • the poor solvent is not particularly limited as long as it is miscible with water and has a lower solubility of the cyclic compound than water.
  • an arbitrary step other than the above may be added to this embodiment.
  • the method for producing a cyclic compound or a derivative thereof is a first drying step, which is a drying step of subjecting a raw material solution containing the cyclic compound or a derivative thereof to a drying treatment to obtain a dried product.
  • the first solution is prepared so that the abundance of the cyclic compound or its derivative in the first solution is smaller than the abundance of ions of the cyclic compound or its derivative.
  • the cyclic compound or its derivative is used as an adsorption medium in the adsorption treatment. It is possible to suppress the adsorption to the compound. As a result, it is possible to suppress a decrease in the yield of the final cyclic compound. Further, by going through these steps, the energy required for purifying the cyclic compound can be reduced, so that the energy required for extracting the highly pure cyclic compound can be reduced.
  • the abundance of the cyclic compound or its derivative in the second solution after the adsorption step is the cyclic compound or its derivative.
  • the second solution is prepared so that the amount of the ions is equal to or greater than the abundance of the ions.
  • the first solution and the second solution are prepared, respectively, so that the pH of the first solution to be subjected to the adsorption treatment is higher than the pH of the second solution that has undergone the adsorption step.
  • pH affects the abundance ratio of the cyclic compound in each solution and the ion abundance ratio of the cyclic compound in each solution.
  • the pH dependence of the abundance ratio of the cyclic compound and the pH dependence of the abundance ratio of the ions satisfy the opposite relationship with each other. Therefore, by manipulating the pH, the magnitude relationship as described above can be easily satisfied between the abundance of the cyclic compound and the abundance of ions. As a result, the yield of the cyclic compound can be easily increased.
  • FIG. 3 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to a third embodiment of the present invention.
  • the method for producing the cyclic compound or its derivative according to the present embodiment includes a raw material liquid preparation step S01, a first drying step S02, a redissolving step S03, an adsorption step S04, a second drying step S05, and an extraction step. It has S06, a crystallization step S07, and a solid-liquid separation step S08.
  • the method for producing a cyclic compound of the present embodiment can also produce a solid, high-purity cyclic compound or a derivative thereof in a high yield.
  • each step will be described in sequence. Since the raw material liquid preparation step S01 is the same step as the raw material liquid preparation step S01 of the first embodiment described above, the description thereof will be omitted.
  • First drying step S02 The raw material liquid obtained in the raw material liquid preparation step S01 is dried to obtain a dried product (dry solid).
  • Examples of the method for drying the raw material liquid include the above-mentioned boiling drying method, spray drying method, heat transfer drying method, infrared drying method, warm air drying method, vacuum drying method and the like. Further, a plurality of types of drying methods including these drying methods may be applied in combination. As for the four typical drying methods, the boiling drying method, the spray drying method, the heat transfer drying method, and the vacuum drying method, each method described in the second embodiment described above can be used.
  • Redissolution step S03 the obtained dried product is dissolved in a solvent to prepare a solution.
  • the adsorption step described later becomes possible.
  • the solvent a good solvent that dissolves the dried product is used.
  • the good solvent include water, methanol, hexane, chloroform and the like.
  • Adsorption step S04 the solution is subjected to an adsorption treatment, but prior to that, a treatment for ionizing the cyclic compound contained in the solution may be performed.
  • This treatment is a treatment for increasing the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound.
  • the abundance ratio of the cyclic compound in the solution can be reduced.
  • the conditions of the solution to be changed include, for example, the pH of the solution, the temperature of the solution, and the like.
  • an acid or an alkali is added to the solution.
  • the pH can be increased by adding alkali. This makes it possible to increase the ionization rate of the cyclic compound in the solution.
  • the addition of acid can lower the pH. As a result, the ionization rate of the cyclic compound in the solution decreases, and conversely, the abundance ratio of the cyclic compound increases.
  • the pH of the solution after the addition of the alkali is preferably about 5.0 to 7.5, and more preferably about 5.5 to 6.5. This makes it possible to reduce the abundance ratio of the cyclic compound in the solution. As a result, the probability that the cyclic compound is adsorbed on the adsorption medium can be reduced in the adsorption treatment described later.
  • the alkali include sodium hydroxide, potassium hydroxide and the like.
  • Examples of the acid include formic acid, acetic acid, hydrochloric acid, propionic acid, butyric acid, valeric acid and the like.
  • the adsorption treatment is a treatment in which the adsorption medium is brought into contact with the solution and the polymer components and the like in the solution are adsorbed on the adsorption medium.
  • impurities in the solution for example, organic components of the polymer are removed.
  • the purity of the finally obtained cyclic compound can be increased and coloring can be suppressed.
  • what is adsorbed and removed in the adsorption treatment is not limited to the organic component of the polymer, and any impurity may be used.
  • the adsorption medium is not particularly limited as long as it has an adsorptive ability, but is, for example, activated carbon, silica gel, zeolite, or the like. Then, in the adsorption treatment, any method is used as long as the adsorption medium can be brought into contact with the solution.
  • the temperature of the solution in the adsorption treatment is, for example, about 30 to 150 ° C.
  • the time of the adsorption treatment is not particularly limited, but is preferably about 10 minutes to 10 hours.
  • the amount of activated carbon added to 100 g of the solution is not particularly limited, but is preferably 0.01 to 3.0 g, more preferably 0.1 to 1.0 g. .. As a result, impurities can be adsorbed with a high probability, the purity of the final cyclic compound can be increased, and coloring can be suppressed.
  • this step may be performed as needed or may be omitted.
  • the order of the adsorption steps is not limited to this embodiment, and may be, for example, before the first drying step or between the extraction step and the crystallization step.
  • the adsorption medium after the adsorption treatment is removed by a solid-liquid separation treatment such as filtration.
  • Second drying step S05 Next, the solution that has undergone the adsorption step is dried to obtain a dried product, but prior to that, a treatment for deionizing the ions of the cyclic compound contained in the solution may be performed.
  • This treatment is a treatment for lowering the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be increased. As a result, the yield of the cyclic compound can be increased in the subsequent extraction step.
  • Examples of the treatment for lowering the ionization rate include a treatment for adding an acid.
  • the pH of the solution after the addition of the acid is preferably about 2.0 to 4.5, more preferably about 2.5 to 3.5. This makes it possible to increase the abundance ratio of the cyclic compound in the solution. As a result, the yield of the cyclic compound can be increased in the extraction step described later.
  • a concentration treatment may be performed separately from or in combination with the treatment for lowering the ionization rate. As a result, the time required for drying can be shortened and the required energy can be reduced. This concentration treatment can be performed under the conditions described above.
  • the solution that has undergone the adsorption step is dried.
  • the second drying step may be performed in the same manner as the first drying step described above, but the method may be the same as or different from the first drying step.
  • Extraction step S06 in the same manner as in the first embodiment described above, the dried product is subjected to a solid-liquid extraction treatment with a solvent for solid-liquid extraction (extraction solvent) to obtain an extract.
  • Crystallization step S07 the extract is subjected to a crystallization treatment to precipitate the solute of the extract as a solid.
  • a crystallization treatment a cyclic compound is precipitated by lowering the solubility of the solute in the extract. Therefore, a highly pure cyclic compound is recovered by undergoing a subsequent solid-liquid separation step. can do. Therefore, a highly pure cyclic compound can be produced in a high yield.
  • the crystallization treatment according to the present embodiment is a treatment in which the temperature of the extract is controlled so that the concentration of the cyclic compound with respect to the solvent in the extract is located in the metastable region.
  • FIG. 4 is a diagram for explaining the crystallization treatment according to the third embodiment of the present invention, in which the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract. It is a figure which shows the relationship between these.
  • FIG. 4 is an example when shikimic acid is used as a cyclic compound which is a solute contained in the extract and methanol is used as a solvent for solid-liquid extraction.
  • the solid line curve shown in FIG. 4 is the persolubility curve of the cyclic compound in the extract.
  • This persolubility curve is a curve obtained by experiments from the relationship between the persolubility of the cyclic compound and the temperature.
  • the hypersolubility refers to the concentration at which crystals start to precipitate spontaneously at that temperature. In other words, it is the lowest concentration at which primary nucleation occurs. Therefore, the concentration region exceeding the persolubility at each temperature is an unstable region where primary nucleation is likely to occur. In the unstable region, crystals are likely to precipitate rapidly, so that impurities are likely to be involved. Therefore, there is a concern that the purity of the precipitated cyclic compound may decrease.
  • the temperature of the extract when the temperature of the extract is manipulated in the crystallization treatment, the temperature of the extract is manipulated so that the relationship between the solubility of the cyclic compound in the extract and the temperature is located in the metastable region.
  • the crystallization treatment is started from the state C1 in which the extract is heated to 60 ° C.
  • State C1 is located in the metastable region. That is, at a temperature of 60 ° C., the concentration of shikimic acid with respect to methanol is higher than the solubility and lower than the hypersolubility.
  • the temperature of the extract is raised by 10 ° C. from the state C1.
  • the boiling point of methanol which is a solvent, is exceeded. Therefore, in the extract, the volatilization of methanol proceeds.
  • the extract is concentrated, so that the concentration of the extract gradually increases.
  • the temperature reaches 70 ° C., the state shifts to the state C2.
  • This state C2 is also located in the metastable region.
  • the temperature of the extract is lowered by 10 ° C. from the state C2.
  • the cooling rate at this time is not particularly limited, but is about 0.1 ° C./min or more and 5.0 ° C./min or less.
  • shikimic acid can be efficiently precipitated while suppressing the inclusion of impurities, so that high-purity shikimic acid can be finally obtained with high productivity.
  • the state shifts to the state C3. This state C3 is also located in the metastable region.
  • the seed crystal of shikimic acid is added to the extract in the state C3.
  • the seed crystal becomes a nucleus in the crystallization treatment and is used to promote the crystallization of shikimic acid.
  • the seed crystal for example, powdery, granular, or lumpy crystals are used. The addition of seed crystals may be performed as needed or may be omitted.
  • the extract is left for a predetermined time from the state C3.
  • shikimic acid is precipitated with the seed crystal as the nucleus.
  • the state shifts to the state C4.
  • This state C4 is also located in the metastable region.
  • the time for leaving the extract to stand is not particularly limited, and is appropriately determined based on the precipitation rate of shikimic acid. As an example, it is preferably about 3 hours or more and 72 hours or less, and more preferably about 10 hours or more and 48 hours or less.
  • the concentration of the extract can be made uniform, and the precipitation rate of shikimic acid is less likely to decrease. Then, high-purity shikimic acid can be efficiently precipitated.
  • the temperature of the extract is lowered by 20 ° C. from the state C4.
  • the cooling rate at this time is also preferably within the above-mentioned range.
  • the state shifts to the state C5.
  • This state C5 is also located in the metastable region.
  • the extract is left for a predetermined time from the state C5.
  • the crystals of shikimic acid contained in the extract grow further, or new crystals are precipitated.
  • the state shifts to the state C6.
  • This state C6 is also located in the metastable region.
  • the time for leaving the extract to stand is not particularly limited, and is appropriately determined based on the precipitation rate of shikimic acid. As an example, it is preferably within the above range.
  • the temperature of the extract is lowered by 30 ° C. from the state C6.
  • the cooling rate at this time is also preferably within the above-mentioned range.
  • the state shifts to the state C7.
  • This state C7 is also located in the metastable region.
  • the extract is left for a predetermined time from the state C7.
  • the crystals of shikimic acid contained in the extract grow further, or new crystals are precipitated.
  • the state shifts to the state C8.
  • This state C8 is also located in the metastable region.
  • the time for leaving the extract to stand is not particularly limited, and is appropriately determined based on the precipitation rate of shikimic acid. As an example, it is preferably within the above range.
  • a series of temperature operations can be performed so as to follow the path from the state C1 to the state C8 as described above, and finally most of the cyclic compounds contained in the extract can be precipitated.
  • the above-mentioned first drying step, redissolving step, adsorption step, second drying step and extraction step may be performed as needed.
  • the raw material liquid prepared in the raw material liquid preparation step is already a cyclic compound. These steps may be omitted if the liquid is contained in a purified state.
  • the crystallization step is a step of precipitating the cyclic compound from the raw material liquid. Therefore, the above-mentioned raw material liquid and various liquids such as a solution and an extract obtained by starting from the raw material liquid can be regarded as the raw material liquid.
  • the method for producing a cyclic compound or a derivative thereof is a cyclic compound from the raw material liquid by a crystallization treatment for controlling the temperature of the raw material liquid containing the cyclic compound or its derivative and a solvent. It has a crystallization step of precipitating a compound or a derivative thereof.
  • the crystallization treatment is a treatment in which the temperature of the raw material liquid is controlled so that the concentration of the cyclic compound or its derivative with respect to the solvent is located in the metastable region.
  • the method for producing a cyclic compound or a derivative thereof according to the present embodiment finally obtains a high-purity cyclic compound in a high yield through a solid-liquid separation step described later. It can be recovered. In addition, since it can be efficiently recovered, the energy required for recovery can be reduced, which is useful from the viewpoint of energy efficiency.
  • the crystallization treatment may be a batch treatment or a continuous treatment. Further, for the crystallization treatment, for example, a known stirring tank can be used.
  • the crystallization treatment according to the present embodiment includes an operation of lowering the temperature of the extract which is the raw material liquid and an operation of stirring the extract.
  • the cyclic compound can be precipitated from the extract without waste with a relatively simple operation.
  • a high-purity cyclic compound can be finally recovered in a high yield.
  • the operation of lowering the temperature of the extract and the operation of stirring the extract are performed three times each, but the number of times is not particularly limited, and even if it is two times or less, it is four times. It may be the above. However, from the viewpoint of further increasing the yield, it is preferably 2 times or more, and more preferably 3 times or more.
  • the maximum reduction width in the operation of lowering the temperature is not particularly limited, and is appropriately selected according to the number of operations.
  • the temperature is preferably 50 ° C. or lower, and more preferably 5.0 ° C. or higher and 40 ° C. or lower. This makes it possible to control the temperature according to the slope of the solubility curve or the persolubility curve, and it is possible to suppress a decrease in purity by preventing abrupt crystallization.
  • the temperature of the extract and the concentration of the cyclic compound in the extract may be continuously monitored and fed back to the temperature operation.
  • the operation may be performed based on the actual results of. This makes it possible to monitor the temperature and concentration in real time and operate according to the monitoring result. This makes it possible to precipitate a highly pure cyclic compound while further shortening the overall required time.
  • two or more operations may be performed simultaneously in time.
  • the operation of lowering the temperature of the extract and the operation of stirring the extract may be performed simultaneously in time.
  • the total required time can be further shortened.
  • the crystallization treatment according to the present embodiment includes an operation of adding a seed crystal of a cyclic compound or a derivative thereof to be precipitated to the extract which is the raw material liquid, as described above.
  • crystallization of the cyclic compound can be promoted even in the metastable region. As a result, a higher-purity cyclic compound can be precipitated.
  • Solid-liquid separation step S08 Next, in the same manner as in the first embodiment described above, the extract in which the cyclic compound is precipitated is subjected to a solid-liquid separation treatment.
  • Examples of other steps additionally provided include a series of steps of sequentially performing the same steps as the above-mentioned redissolving step and adsorption step, and then performing a reprecipitation step.
  • the reprecipitation step is a step of sequentially performing the same steps as the redissolution step and the same steps as the adsorption step, and then adding a poor solvent to the obtained solution.
  • a poor solvent By adding the poor solvent, precipitation of the cyclic compound can be obtained in the solution.
  • a cyclic compound having further increased purity By subjecting this precipitate to the same step as the solid-liquid separation step, a cyclic compound having further increased purity can be obtained.
  • the poor solvent is not particularly limited as long as it is miscible with water and has a lower solubility of the cyclic compound than water.
  • an arbitrary step other than the above may be added to this embodiment.
  • cyclic compound or derivative thereof an example of the cyclic compound produced by the method for producing a cyclic compound according to the above-described embodiment will be described.
  • a cyclic compound is, for example, a compound represented by the following formula (1).
  • Examples of the 5-membered ring of the saturated ring, the partially saturated ring or the aromatic ring include a furan structure, a thiophene structure, a pyrrole structure, a pyrrolidine structure, a tetrahydrofuran structure, a 2,3-dihydrofuran structure, a pyrazole structure, an imidazole structure and an oxazole structure.
  • Examples thereof include an isooxazole structure, a thiazole structure, and an isothiazole structure.
  • Examples of the 6-membered ring of the saturated ring include a hydrocarbon-based saturated ring such as a cyclohexane structure, a piperidine structure, a piperazine structure, a triadinan structure, a tetradinane structure, a pentadinane structure, and a nitrogen-containing saturated ring such as a quinuclidine structure, and a tetrahydropyran structure.
  • An oxygen-containing saturated ring such as a morpholine structure, a sulfur-containing saturated ring such as a tetrahydropyran structure, and the like.
  • the 6-membered ring of the partially saturated ring includes a cyclohexene structure, a hydrocarbon-based partially saturated ring such as a cyclohexadiene structure, a nitrogen-containing partially saturated ring such as a piperidine structure, an oxygen-containing partially saturated ring such as a pyran structure, and a thiazine structure.
  • a cyclohexene structure such as a cyclohexadiene structure
  • a nitrogen-containing partially saturated ring such as a piperidine structure
  • an oxygen-containing partially saturated ring such as a pyran structure
  • thiazine structure such as sulfur-containing partially saturated ring and the like can be mentioned.
  • the 6-membered ring of the aromatic ring includes a hydrocarbon-based aromatic ring such as a benzene structure, a pyridine structure, a pyridazine structure, a pyrimidine structure, a pyrazine structure, a triazine structure, a tetrazine structure, and a nitrogen-containing aromatic ring (nitrogen-containing structure) such as a pentazine structure. (Unsaturated ring) and the like.
  • a hydrocarbon-based aromatic ring such as a benzene structure, a pyridine structure, a pyridazine structure, a pyrimidine structure, a pyrazine structure, a triazine structure, a tetrazine structure, and a nitrogen-containing aromatic ring (nitrogen-containing structure) such as a pentazine structure. (Unsaturated ring) and the like.
  • fused ring of the two 6-membered rings examples include quinoline-based structures such as quinoline, isoquinoline, quinolizidine, quinoxaline, cinnoline, quinazoline, phthalazine, diazanaphthalene, and pteridine.
  • X is a single bond or a bond containing one or more carbon atoms.
  • the oxygen atom is directly bonded to the ring-constituting atom of ring A.
  • examples of the bond containing one or more carbon atoms include a hydrocarbon group having 1 to 4 carbon atoms, an ether bond, an ester bond, an amide bond, a carbonyl group, a vinylidene group, and the like, and one of them. It is considered to be a species or a combination of two or more species.
  • Y is a hydrogen atom or an alkyl group.
  • the number of carbon atoms of the alkyl group is preferably 1 to 12, and more preferably 1 to 4.
  • R 2 to R 6 are independently hydrogen atoms, hydroxyl groups, amino groups, alkoxy groups, carboxyl groups or carbonyl groups.
  • R 2 to R 5 are independently hydrogen atoms, hydroxyl groups, amino groups, alkoxy groups, carboxyl groups or carbonyl groups.
  • R 2 to R 6 when the ring A is a 6-membered ring , or any of R 2 to R 5 when the ring A is a 5-membered ring is a carbonyl group
  • the ring is a ring.
  • a carbonyl group refers to a structure in which the ring-constituting atom of A is a carbon atom and the carbon atom and the oxygen atom have a double bond.
  • cyclic compound examples include benzoic acid, phthalic acid, isophthalic acid, terephthalic acid, hemmellitic acid, trimellitic acid, trimesic acid, melophonic acid, planar acid, pyromellitic acid, phenylacetic acid and hydroxyphenylacetic acid.
  • Phenylbutyric acid (phenyllactate), hydroxyphenylbutyric acid, phenylpyrvic acid, hydroxyphenylpyrvic acid, phenyllactic acid, hydroxyphenyllactic acid, anthranilic acid, hydroatropic acid, atropic acid, hydrosilicic acid (kumalic acid), silicic acid, salicylic acid (2-Hydroxybenzoic acid), m-salicylic acid (3-hydroxybenzoic acid), p-salicylic acid (4-hydroxybenzoic acid), methoxybenzoic acid, aminobenzoic acid, hydroxybenzoic acid, pyrocatechuic acid (2,3-dihydroxy) Benzoic acid), ⁇ -resorcilic acid (2,4-dihydroxybenzoic acid), gentidic acid (2,5-dihydroxybenzoic acid), ⁇ -resorcilic acid (2,6-dihydroxybenzoic acid), protocatechuic acid (3,4) -Dihydroxybenzo
  • Acids isophthalonic acid, terephthalonic acid, atrolactinic acid, tropic acid, melirot acid, floret acid, dihydrocaffeic acid, hydroferulic acid, hydroisoferulic acid, umbiliic acid, caffeic acid (coffee acid), ferulic acid, isoferulic acid, Examples thereof include synapic acid, syringic acid, dehydroquinic acid, dehydroshikimic acid, shikimic acid, corismic acid, L-tryptophan, L-tyrosine, prefenic acid, allogenic acid, L-phenylalanine and the like.
  • cyclic compound flavonoids, lignans, chalcones, stilbenoids, alkaloids, curcuminoids, terpenoids, saponins, various glycosides, polyphenols such as various polyphenol aromatic compounds, as well as amino acids, Examples include vitamins.
  • flavonoids include, for example, aurantidin, cyanidin, delphinidin, Europeanidin, luteolinidin, pelargonidin, malvidin, peonidin, petunidin, anthocyanidin such as rosinidin, anthocyanidin such as procyanidin, naringenin, eriocitrin, pinosembrin, Flavanones such as thiol, flavans such as catechin, apigenin, luteolin, baicalene, flavones such as chrycin, quercetin, flavonols such as kempferol, isoflavones, isoflavans, isoflavandiols, isoflavonoids such as genistein, etc. Examples thereof include neo-flavonoids, biflavonoids, aurones, prenyl flavonoids, and O-methylated flavonoids.
  • lignans examples include pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, cilingalesinol, sesamin, arctigenin, sesaminol, podophyllotoxin, and steganacin.
  • curcuminoids examples include curcumin and ginger.
  • aromatic compounds include vanillin, 2-phenylethanol, phenylacetic acid, synamic alcohol, isoeugenol, ferulic acid, 4-aminobenzoic acid, anetol, estragor, methyl anthranilate, and methyl cinnamic acid.
  • Examples of the alicyclic compound include carveol, perilla alcohol, borneol, methyl jasmonate, 1,8-cineole, L-menthone, valencene, nootkatone, ⁇ -pinene, camphene, L-carboxylic, perillaaldehyde, and myltenal. , L-menthyl acetate, ⁇ -ionone and the like.
  • examples of the aliphatic compound include cis-3-hexenol, cis-3-hexenyl acetate, acetoin, nerol, farnesol, arginine, muconic acid and the like.
  • examples of the derivative of the cyclic compound include esters, acid anhydrides, amides, acid halides, salts and the like of the above-mentioned compounds, or all compounds derived from the cyclic compound.
  • the molecular weight of the cyclic compound or its derivative is not particularly limited, but is preferably 120 to 1000, and more preferably 130 to 800.
  • Ring A cyclic compound represented by the above formula (1) is, when the ring constituent atoms are all 5-membered ring saturated ring or partially saturated ring are carbon atoms, R 2 ⁇ R 5 and X It is preferable that one or more of the carbon atoms of the ring A to be bonded are asymmetric carbon atoms. Also, Ring A cyclic compound represented by the above formula (1) is, when the ring constituent atoms are all 6-membered ring saturated ring or partially saturated ring are carbon atoms, R 2 ⁇ R 6 and X It is preferable that one or more of the carbon atoms of the ring A to be bonded are asymmetric carbon atoms.
  • the cyclic compound becomes a stereoisomer.
  • the carbon atom of the ring A to which X is bonded is C 1
  • the carbon atom of the ring A to which R 2 is bonded is C 2
  • the ring to which R 3 is bonded is bonded.
  • the carbon atom of A is C 3
  • the carbon atom of ring A to which R 4 is bonded is C 4
  • the carbon atom of ring A to which R 5 is bonded is C 5
  • the carbon atom of ring A to which R 6 is bonded is C 5.
  • a combination of these carbon atoms is an asymmetric carbon atom is preferably one selected from the group consisting of the following (a) ⁇ (h).
  • ring A is a 5-membered ring of a saturated ring, a partially saturated ring or an aromatic ring, or a 6-membered ring of a partially saturated ring or an aromatic ring
  • X is a single bond or one or more rings. It is a bond containing the number of carbon atoms
  • Y is a hydrogen atom or an alkyl group
  • R 2 to R 6 R 2 to R 5 when the ring A is a 5-membered ring
  • C 1 to C 6 are carbon atoms as ring constituent atoms of ring A, respectively.
  • the cyclic compound and its derivative are compounds represented by the above formula (2), and in particular, 3-dehydroquinate, 3-dehydroshikimic acid, shikimic acid, chorismic acid or prephenic acid. preferable. These compounds are compounds used in many fields, and their structures are represented by the following formulas.
  • the uses of the above cyclic compounds or derivatives thereof are not particularly limited, but for example, fragrance compositions, cosmetic compositions, pharmaceuticals, pesticides, chemicals, materials for electrical and electronic parts, synthetic fibers, resins, etc.
  • Examples include various chemical products such as food additives.
  • the cyclic compound or its derivative is also used as a raw material for various chemical products. Examples of this raw material include fragrance raw materials, cosmetic raw materials, pharmaceutical raw materials, agricultural chemical raw materials, chemical raw materials, electric / electronic parts raw materials, synthetic fiber raw materials, resin raw materials, food additive raw materials and the like.
  • the raw material refers to an intermediate used for the synthesis of chemical products.
  • the grown transformant was reacted with a mixed sugar to obtain a culture solution.
  • the obtained culture solution was centrifuged to obtain a supernatant solution (raw material liquid).
  • the concentration of the solute in the raw material liquid was 7% by mass.
  • the purity of shikimic acid, that is, the ratio of the mass of shikimic acid to the total mass of the solute was 48%.
  • the obtained raw material liquid was dried by a vacuum drying method to obtain a dried product (first drying step).
  • the drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
  • the obtained dried product was redissolved in pure water to obtain a solution.
  • the amount of pure water used for redissolution was 5 g with respect to 1 g of the dried product.
  • the pH-adjusted solution was dried by a vacuum drying method to obtain a dried product (second drying step).
  • the drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
  • the dried product was subjected to a solid-liquid extraction treatment to obtain an extract.
  • Methanol was used as the solvent for solid-liquid extraction.
  • the temperature of the solid-liquid extraction treatment was 30 ° C., the time was 2 hours, and the amount of the solvent was 20 g with respect to 1 g of the dried product.
  • the obtained extract was subjected to crystallization treatment to precipitate shikimic acid (cyclic compound).
  • the temperature was controlled so that the temperature and concentration of the extract were located within the metastable region.
  • Example 2A-4A Shikimic acid was recovered in the same manner as in Example 1A except that the heating temperatures in the first drying step and the second drying step were changed as shown in Table 1.
  • Example 5A Shikimic acid was recovered in the same manner as in Example 1A except that the adsorption step, the second drying step, and the extraction step were omitted.
  • Example 6A Shikimic acid was recovered in the same manner as in Example 1A except that the second drying step was omitted and the extraction step was changed to a liquid-liquid extraction treatment.
  • 1-butanol was used as a solvent for liquid-liquid extraction.
  • the temperature at the time of extraction was 30 ° C., and the extraction time was 2 hours. Further, the mass of the liquid-liquid extraction solvent used was 5 g with respect to 1 g of the solution that had undergone the adsorption step.
  • Example 7A Shikimic acid was recovered in the same manner as in Example 1A except that the second drying step was changed to drying by the spray drying method.
  • Example 8A Shikimic acid was recovered in the same manner as in Example 7A except that the crystallization treatment in the precipitation step was changed to concentrated dry solid.
  • the pH of the obtained first solution was adjusted to 6.0 so that the abundance of the compound in the first solution was smaller than the abundance of ions.
  • the first solution was treated with activated carbon (adsorption step).
  • 0.4 g of activated carbon was used with respect to 100 g of the first solution.
  • the pH of the second solution treated with activated carbon was adjusted to 3.0 so that the abundance of the compound in the second solution was equal to or greater than the abundance of ions.
  • Example 5B Shikimic acid was recovered in the same manner as in Example 1B except that the second drying step was omitted and the extraction step was changed to a liquid-liquid extraction treatment.
  • 1-butanol was used as a solvent for liquid-liquid extraction.
  • the temperature at the time of extraction was 30 ° C., and the extraction time was 2 hours. Further, the mass of the liquid-liquid extraction solvent used was 5 g with respect to 1 g of the solution that had undergone the adsorption step.
  • Example 8B Shikimic acid was recovered in the same manner as in Example 1B except that the second drying step was changed to drying by the spray drying method.
  • the grown transformant was reacted with a mixed sugar to obtain a culture solution.
  • the obtained culture solution was centrifuged to obtain a supernatant solution (raw material liquid).
  • the concentration of the solute in the raw material liquid was 7% by mass.
  • the purity of shikimic acid, that is, the ratio of the mass of shikimic acid to the total mass of the solute was 48%.
  • the obtained raw material liquid was dried by a vacuum drying method to obtain a dried product (first drying step).
  • the drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
  • the pH of the obtained solution was adjusted to 6.0. Subsequently, the solution was treated with activated carbon (adsorption step). In addition, 0.4 g of activated carbon was used with respect to 100 g of the solution. Subsequently, the pH of the activated carbon-treated solution was adjusted to 3.0.
  • the pH-adjusted solution was dried by a vacuum drying method to obtain a dried product (second drying step).
  • the drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
  • the obtained extract was subjected to crystallization treatment to precipitate shikimic acid (cyclic compound).
  • the crystallization treatment the operation of changing the temperature of the extract and the operation of stirring the extract were repeated from the state C1 to the state C8 shown in FIG. That is, the temperature was manipulated so that the temperature and the concentration of the cyclic compound in the extract were located within the metastable region shown in FIG.
  • Example 9C Shikimic acid was recovered in the same manner as in Example 1C except that the adsorption step, the second drying step, and the extraction step were omitted.
  • Example 10C Shikimic acid was recovered in the same manner as in Example 1C except that the second drying step was omitted and the extraction step was changed to a liquid-liquid extraction treatment.
  • 1-butanol was used as a solvent for liquid-liquid extraction.
  • the temperature at the time of extraction was 30 ° C., and the extraction time was 2 hours. Further, the mass of the liquid-liquid extraction solvent used was 5 g with respect to 1 g of the solution that had undergone the adsorption step.
  • a high-purity cyclic compound could be precipitated in a high yield. Therefore, even after the final solid-liquid separation step, a high-purity cyclic compound can be recovered in a high yield.
  • the yield could be increased by repeating the operation of lowering the temperature of the extract and the operation of stirring the extract three times or more.
  • the first drying step using a vacuum drying method of heating in an appropriate temperature range since the first drying step using a vacuum drying method of heating in an appropriate temperature range is provided, a high-purity cyclic compound is finally recovered in a high yield. can do. Further, by passing through the first drying step, the extraction step and the precipitation step, the organic component and the inorganic component which are impurities can be sequentially removed, and from this viewpoint as well, high purity and high yield can be achieved. .. Furthermore, the whiteness of the obtained cyclic compound can be increased. Further, in the vacuum drying method, the drying treatment can be performed in a particularly short time, and the energy required for extracting the cyclic compound can be reduced by utilizing extraction and precipitation. As a result, a high-purity cyclic compound or a derivative thereof can be produced in a high yield. Therefore, the present invention has industrial applicability.

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Abstract

In a preferred embodiment, this production method for a cyclic compound or a derivative thereof has: a drying step for subjecting a feedstock liquid containing the cyclic compound or the derivative thereof to a drying treatment to obtain a dried product; an extraction step for extracting the cyclic compound or the derivative thereof from the dried product into an extraction solvent to obtain an extraction solution; and a precipitation step for precipitating the cyclic compound or the derivative thereof from the extraction solution. The drying treatment is a treatment in which the feedstock liquid is heated at a temperature of 65-125°C under a pressure of 10 Pa or less.

Description

環式化合物またはその誘導体の製造方法Method for producing cyclic compound or derivative thereof
　本発明は、環式化合物またはその誘導体の製造方法に関するものである。 The present invention relates to a method for producing a cyclic compound or a derivative thereof.
　環式化合物は、香料や化粧品またはその原料、樹脂や薬品またはその原料等に用いられている。近年、化石資源の枯渇や二酸化炭素濃度の増加に伴う地球温暖化への懸念から、バイオマス資源を原料として環式化合物を製造することが試みられている。 Cyclic compounds are used in fragrances and cosmetics or their raw materials, resins and chemicals or their raw materials, and the like. In recent years, due to concerns about global warming due to the depletion of fossil resources and the increase in carbon dioxide concentration, attempts have been made to produce cyclic compounds using biomass resources as a raw material.
　例えば、特許文献１には、バイオマスから微生物発酵によりメタンを製造した後、触媒反応によってメタンからベンゼンを製造し、さらにこのベンゼンからベンゼン誘導体を製造する方法が開示されている。このようにして製造されたベンゼン誘導体は、芳香族ポリマーの原料として用いられるため、化石資源に依存しないポリマーを実現することができる。 For example, Patent Document 1 discloses a method of producing methane from biomass by microbial fermentation, then producing benzene from methane by a catalytic reaction, and further producing a benzene derivative from this benzene. Since the benzene derivative produced in this manner is used as a raw material for an aromatic polymer, it is possible to realize a polymer that does not depend on fossil resources.
特開２００４－１２３６６６号公報Japanese Unexamined Patent Publication No. 2004-123666
　しかしながら、従来の方法は、ベンゼン誘導体の製造効率がまだ十分ではない。具体的には、バイオマスからメタンおよびベンゼンを経てフタル酸等のベンゼン誘導体を製造する際、投入する手間やエネルギーの割に、合成されるベンゼン誘導体の量が少ないという問題がある。 However, the conventional method does not yet have sufficient efficiency in producing benzene derivatives. Specifically, when producing a benzene derivative such as phthalic acid from biomass via methane and benzene, there is a problem that the amount of benzene derivative synthesized is small for the labor and energy input.
　また、製造されるベンゼン誘導体の純度を高めることも求められている。特許文献１にはベンゼンを蒸留法等で精製することが開示されており、これによってベンゼン誘導体の純度を高めることが可能であるものの、その際にはやはり多くのエネルギーを消費する。 It is also required to increase the purity of the produced benzene derivative. Patent Document 1 discloses that benzene is purified by a distillation method or the like, and although it is possible to increase the purity of the benzene derivative by this, a large amount of energy is still consumed in that case.
　本発明の目的は、高純度の環式化合物またはその誘導体を高い収率で製造可能な製造方法を提供することにある。 An object of the present invention is to provide a production method capable of producing a high-purity cyclic compound or a derivative thereof in a high yield.
　このような目的は、下記（１）～（１１）の本発明により達成される。
　（１）　環式化合物またはその誘導体を含有する原料液体に乾燥処理を施し、乾燥物を得る乾燥工程と、
　前記乾燥物から前記環式化合物またはその誘導体を抽出用溶媒に抽出し、抽出液を得る抽出工程と、
　前記抽出液から前記環式化合物またはその誘導体を析出させる析出工程と、
を有し、
　前記乾燥処理は、圧力１０Ｐａ以下において前記原料液体を温度６５～１２５℃で加熱する処理であることを特徴とする環式化合物またはその誘導体の製造方法。 Such an object is achieved by the present invention of the following (1) to (11).
(1) A drying step of subjecting a raw material liquid containing a cyclic compound or a derivative thereof to a drying treatment to obtain a dried product, and
An extraction step of extracting the cyclic compound or a derivative thereof from the dried product into an extraction solvent to obtain an extract, and
A precipitation step of precipitating the cyclic compound or its derivative from the extract, and
Have,
A method for producing a cyclic compound or a derivative thereof, wherein the drying treatment is a treatment of heating the raw material liquid at a temperature of 65 to 125 ° C. at a pressure of 10 Pa or less.
　（２）　前記乾燥工程と前記抽出工程との間に設けられ、前記乾燥物を再溶解用溶媒に溶解させ、再溶解液を調製する再溶解工程と、
　前記再溶解工程と前記抽出工程との間に設けられ、前記再溶解液に吸着処理を施す吸着工程と、
をさらに有する上記（１）に記載の環式化合物またはその誘導体の製造方法。 (2) A redissolving step provided between the drying step and the extraction step, in which the dried product is dissolved in a solvent for redissolving to prepare a redissolving solution, and
An adsorption step provided between the redissolving step and the extraction step and adsorbing the redissolving liquid, and an adsorption step.
The method for producing a cyclic compound or a derivative thereof according to (1) above.
　（３）　環式化合物またはその誘導体を含有する原料液体に乾燥処理を施し、乾燥物を得る乾燥工程と、
　前記乾燥物を第１溶媒に再溶解し、第１溶液を得る再溶解工程と、
　前記第１溶液に対し、吸着体への吸着処理を施すことにより、第２溶液を得る吸着工程と、
　前記第２溶液から前記環式化合物またはその誘導体を析出させる析出工程と、
を有し、
　前記第１溶液における前記環式化合物またはその誘導体の存在量が、前記環式化合物またはその誘導体のイオンの存在量よりも少なくなるように、前記第１溶液を調製することを特徴とする環式化合物またはその誘導体の製造方法。 (3) A drying step of subjecting a raw material liquid containing a cyclic compound or a derivative thereof to a drying treatment to obtain a dried product, and
A re-dissolution step of redissolving the dried product in a first solvent to obtain a first solution, and
An adsorption step of obtaining a second solution by subjecting the first solution to an adsorbent treatment.
A precipitation step of precipitating the cyclic compound or its derivative from the second solution, and
Have,
The first solution is prepared so that the abundance of the cyclic compound or its derivative in the first solution is smaller than the abundance of ions of the cyclic compound or its derivative. A method for producing a compound or a derivative thereof.
　（４）　前記第２溶液における前記環式化合物またはその誘導体の存在量が、前記環式化合物またはその誘導体のイオンの存在量以上になるように、前記第２溶液を調製する上記（３）に記載の環式化合物またはその誘導体の製造方法。 (4) In the above (3), prepare the second solution so that the abundance of the cyclic compound or its derivative in the second solution is equal to or greater than the abundance of ions of the cyclic compound or its derivative. The method for producing a cyclic compound or a derivative thereof.
　（５）　前記第１溶液のｐＨが前記第２溶液のｐＨより大きくなるように、前記第１溶液および前記第２溶液を調製する上記（３）または（４）に記載の環式化合物またはその誘導体の製造方法。 (5) The cyclic compound according to (3) or (4) above, or the cyclic compound thereof, in which the first solution and the second solution are prepared so that the pH of the first solution is higher than the pH of the second solution. Method for producing a derivative.
　（６）　前記乾燥工程の前に設けられ、バイオマスから前記原料液体を調製する原料液体調製工程をさらに有する上記（１）ないし（５）のいずれかに記載の環式化合物またはその誘導体の製造方法。 (6) The method for producing a cyclic compound or a derivative thereof according to any one of (1) to (5) above, which is provided before the drying step and further includes a raw material liquid preparation step for preparing the raw material liquid from biomass. ..
　（７）　前記原料液体調製工程は、前記原料液体を濃縮する濃縮処理を含む上記（６）に記載の環式化合物またはその誘導体の製造方法。 (7) The method for producing a cyclic compound or a derivative thereof according to (6) above, wherein the raw material liquid preparation step includes a concentration treatment for concentrating the raw material liquid.
　（８）　環式化合物またはその誘導体と溶媒とを含有する原料液体の温度を操作する晶析処理により、前記原料液体から前記環式化合物またはその誘導体を析出させる晶析工程を有し、
　前記晶析処理は、前記原料液体における前記環式化合物またはその誘導体の濃度が準安定領域に位置するように、前記原料液体の温度を操作する処理であることを特徴とする環式化合物またはその誘導体の製造方法。 (8) It has a crystallization step of precipitating the cyclic compound or its derivative from the raw material liquid by a crystallization treatment for controlling the temperature of the raw material liquid containing the cyclic compound or its derivative and a solvent.
The crystallization treatment is a treatment for controlling the temperature of the raw material liquid so that the concentration of the cyclic compound or its derivative in the raw material liquid is located in the semi-stable region. Derivative manufacturing method.
　（９）　前記晶析処理は、前記原料液体に、前記環式化合物またはその誘導体の種晶を添加する操作を含む上記（８）に記載の環式化合物またはその誘導体の製造方法。 (9) The method for producing a cyclic compound or its derivative according to (8) above, wherein the crystallization treatment includes an operation of adding a seed crystal of the cyclic compound or its derivative to the raw material liquid.
　（１０）　前記晶析処理は、前記原料液体の温度を低下させる操作と、前記原料液体を撹拌する操作と、を含む上記（８）または（９）に記載の環式化合物またはその誘導体の製造方法。 (10) Production of the cyclic compound or derivative thereof according to (8) or (9) above, wherein the crystallization treatment includes an operation of lowering the temperature of the raw material liquid and an operation of stirring the raw material liquid. Method.
　（１１）　バイオマスから前記原料液体を調製する原料液体調製工程をさらに有する上記（８）ないし（１０）のいずれかに記載の環式化合物またはその誘導体の製造方法。 (11) The method for producing a cyclic compound or a derivative thereof according to any one of (8) to (10) above, further comprising a raw material liquid preparation step for preparing the raw material liquid from biomass.
　本発明によれば、高純度の環式化合物またはその誘導体を高い収率で製造することができる。 According to the present invention, a high-purity cyclic compound or a derivative thereof can be produced in a high yield.
図１は、本発明の第１実施形態に係る環式化合物またはその誘導体の製造方法を説明するための工程図である。FIG. 1 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to the first embodiment of the present invention. 図２は、溶液中の環式化合物の存在比および溶液中の環式化合物のイオンの存在比とｐＨとの関係の一例を示すグラフである。FIG. 2 is a graph showing an example of the relationship between the abundance ratio of a cyclic compound in a solution, the abundance ratio of ions of a cyclic compound in a solution, and pH. 図３は、本発明の第３実施形態に係る環式化合物またはその誘導体の製造方法を説明するための工程図である。FIG. 3 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to a third embodiment of the present invention. 図４は、本発明の第３実施形態に係る晶析処理を説明するための図であって、横軸に抽出液の温度、縦軸に抽出液における環式化合物の溶解度をとったとき、これらの間の関係を示す図である。FIG. 4 is a diagram for explaining the crystallization treatment according to the third embodiment of the present invention, in which the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract. It is a figure which shows the relationship between these. 図５は、比較例に係る晶析処理を説明するための図であって、横軸に抽出液の温度、縦軸に抽出液における環式化合物の溶解度をとったとき、これらの間の関係を示す図である。FIG. 5 is a diagram for explaining the crystallization treatment according to the comparative example, and when the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract, the relationship between them. It is a figure which shows.
　以下、本発明の環式化合物またはその誘導体の製造方法について添付図面に示す好適実施形態に基づいて詳細に説明する。 Hereinafter, the method for producing the cyclic compound of the present invention or a derivative thereof will be described in detail based on the preferred embodiments shown in the accompanying drawings.
　＜第１実施形態＞
１．環式化合物またはその誘導体の製造方法
　まず、本発明の環式化合物またはその誘導体の製造方法の第１実施形態について説明する。
　図１は、本発明の第１実施形態に係る環式化合物またはその誘導体の製造方法を説明するための工程図である。 <First Embodiment>
1. 1. Method for Producing Cyclic Compound or Derivative thereof First, a first embodiment of the method for producing a cyclic compound or its derivative of the present invention will be described.
FIG. 1 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to the first embodiment of the present invention.
　本実施形態に係る環式化合物またはその誘導体の製造方法は、原料液体調製工程Ｓ０１と、第１乾燥工程Ｓ０２と、再溶解工程Ｓ０３と、吸着工程Ｓ０４と、第２乾燥工程Ｓ０５と、抽出工程Ｓ０６と、析出工程Ｓ０７と、固液分離工程Ｓ０８と、を有する。このような環式化合物の製造方法によれば、固体で高純度の環式化合物またはその誘導体を高い収率で製造することができる。以下、各工程について順次説明する。なお、以下の説明では、環式化合物またはその誘導体を省略して「環式化合物」ともいう。また、環式化合物またはその誘導体の製造方法を省略して「環式化合物の製造方法」ともいう。なお、環式化合物については、後に詳述する。 The method for producing the cyclic compound or its derivative according to the present embodiment includes a raw material liquid preparation step S01, a first drying step S02, a redissolving step S03, an adsorption step S04, a second drying step S05, and an extraction step. It has S06, a precipitation step S07, and a solid-liquid separation step S08. According to such a method for producing a cyclic compound, a solid and high-purity cyclic compound or a derivative thereof can be produced in a high yield. Hereinafter, each step will be described in sequence. In the following description, the cyclic compound or its derivative is abbreviated as "cyclic compound". Further, the method for producing a cyclic compound or a derivative thereof is omitted and is also referred to as a "method for producing a cyclic compound". The cyclic compound will be described in detail later.
　１．１．原料液体調製工程Ｓ０１
　まず、バイオマスを用意する。バイオマスとは、植物由来の有機性資源を指す。具体的には、デンプンやセルロース等の形に変換されて蓄えられたもの、植物体を食べて成育する動物の体、植物体や動物体を加工してできる製品等が挙げられる。 1.1. Raw material liquid preparation step S01
First, prepare biomass. Biomass refers to organic resources derived from plants. Specific examples thereof include those that have been converted into starch, cellulose, or the like and stored, the body of an animal that grows by eating a plant, a product that can be processed from a plant or an animal, and the like.
　より具体的には、セルロース系作物（パルプ、ケナフ、麦わら、稲わら、古紙、製紙残渣等）、木材、木炭、堆肥、天然ゴム、綿花、サトウキビ、おから、油脂（菜種油、綿実油、大豆油、ココナッツ油、ヒマシ油等）、炭水化物系作物（トウモロコシ、イモ類、小麦、米、籾殻、米ぬか、古米、キャッサバ、サゴヤシ等）、バガス、そば、大豆、精油（松根油、オレンジ油、ユーカリ油等）、パルプ黒液、生ごみ、植物油カス、水産物残渣、家畜排泄物、食品廃棄物、排水汚泥等が挙げられる。 More specifically, cellulose-based crops (pulp, kenaf, straw, rice straw, used paper, paper residue, etc.), wood, charcoal, compost, natural rubber, cotton, sugar cane, okara, fats and oils (rapeseed oil, cottonseed oil, soybean oil, etc.) , Coconut oil, castor oil, etc.), Carbohydrate crops (corn, potatoes, wheat, rice, rice husks, rice bran, old rice, cassaba, sago palm, etc.), bagasse, buckwheat, soybean, essential oil (pine root oil, orange oil, eucalyptus oil, etc.) Etc.), pulp black liquor, food waste, vegetable oil residue, marine product residue, livestock excrement, food waste, wastewater sludge, etc.
　１．１．１．前処理
　次に、バイオマスに前処理を施し、混合糖を得る。このような前処理としては、例えば、物理的処理、化学的処理、物理化学的処理、生物学的処理等が挙げられ、これらのうちの１種または２種以上を組み合わせた処理が採用される。 1.1.1. Pretreatment Next, the biomass is pretreated to obtain a mixed sugar. Examples of such pretreatment include physical treatment, chemical treatment, physicochemical treatment, biological treatment, and the like, and one or a combination of two or more of these is adopted. ..
　このうち、物理的処理としては、例えば、ディスクミル、グラインダー等による微細化処理、圧縮処理、電磁波照射処理、電子線照射処理等が挙げられる。 Among these, physical processing includes, for example, miniaturization processing by a disk mill, grinder, etc., compression processing, electromagnetic wave irradiation processing, electron beam irradiation processing, and the like.
　また、化学的処理としては、例えば、硫酸、硝酸、塩酸、リン酸、アルカリのようなイオン液体による処理、水熱処理、亜臨界水処理、超臨界流体処理、触媒による処理、酸化剤処理、熱エネルギーを付与する処理、光エネルギーを付与する処理等が挙げられる。 The chemical treatment includes, for example, treatment with ionic liquids such as sulfuric acid, nitric acid, hydrochloric acid, phosphoric acid, and alkali, hydrothermal treatment, subcritical water treatment, supercritical fluid treatment, catalytic treatment, oxidant treatment, and heat. Examples include a process of imparting energy and a process of imparting light energy.
　さらに、物理化学的処理としては、例えば、水蒸気爆砕処理、アンモニア爆砕処理等が挙げられる。 Further, examples of the physicochemical treatment include steam blasting treatment and ammonia blasting treatment.
　また、生物学的処理としては、例えば、菌類、細菌等を用いた処理が挙げられる。
　以上のようにして、混合糖が得られる。得られる混合糖の一例としては、グルコース単位を有するオリゴ糖または多糖類が含まれる。具体的には、グルコース、フルクトース、マンノース、アラビノース、キシロース、ガラクトースのような単糖類、セロビオース、ショ糖、ラクトース、マルトース、トレハロース、セロビオース、キシロビオースのような二糖類、デキストリンまたは可溶性澱粉のような多糖類等が挙げられる。 In addition, examples of biological treatment include treatment using fungi, bacteria, and the like.
As described above, the mixed sugar is obtained. Examples of the resulting mixed sugars include oligosaccharides or polysaccharides having glucose units. Specifically, monosaccharides such as glucose, fructose, mannose, arabinose, xylose, galactose, disaccharides such as cellobiose, sucrose, lactose, maltose, trehalose, cellobiose, xylobiose, polysaccharides such as dextrin or soluble starch. Examples include sugars.
　また、混合糖としては、上記の他に、わら（稲わら、大麦わら、小麦わら、ライ麦わら、オート麦わら等）、バガスのような非可食農産廃棄物、スイッチグラス、ネピアグラス、ミスキャンサス等のエネルギー作物や、木くず、古紙のようなものを、糖化酵素で糖化してなる糖化液、あるいは糖蜜を含むものも用いられる。 In addition to the above, the mixed sugar includes straw (rice straw, barley straw, wheat straw, rye straw, oat straw, etc.), non-edible agricultural waste such as bagasse, switchgrass, napier grass, and miscanthus. Energy crops such as, wood chips, waste paper, etc. are saccharified with saccharifying enzymes, and saccharified liquids, or those containing molasses are also used.
　１．１．２．形質転換処理
　次に、混合糖を含有する反応液中で、形質転換体を培養または反応させて原料液体を調製する。 1.1.2. Transformation treatment Next, the transformant is cultured or reacted in a reaction solution containing a mixed sugar to prepare a raw material liquid.
　１．１．２．１．形質転換体
　形質転換体は、混合糖との反応に先立ち、培地において培養して増殖させることが好ましい。 1.1.2.1. Transformant The transformant is preferably cultured and grown in a medium prior to reaction with the mixed sugar.
　１．１．２．２．培地
　用いられる培地としては、炭素源、窒素源、無機塩類、その他の栄養物質等を含有する天然培地または合成培地が挙げられる。 11.2.2. Medium The medium used includes a natural medium or a synthetic medium containing a carbon source, a nitrogen source, inorganic salts, other nutritional substances and the like.
　培地中における窒素源の濃度は、使用する窒素源によっても異なるが、例えば０．１～１０（ｗ／ｖ％）とされる。 The concentration of the nitrogen source in the medium varies depending on the nitrogen source used, but is, for example, 0.1 to 10 (w / v%).
　培地中における無機塩類の濃度は、使用する無機塩類によっても異なるが、例えば０．０１～１（ｗ／ｖ％）とされる。 The concentration of inorganic salts in the medium varies depending on the inorganic salts used, but is, for example, 0.01 to 1 (w / v%).
　培地中における栄養物質の濃度は、使用する栄養物質によっても異なるが、例えば０．１～１０（ｗ／ｖ％）とされる。 The concentration of the nutritional substance in the medium varies depending on the nutritional substance used, but is, for example, 0.1 to 10 (w / v%).
　さらに、必要に応じて、ビタミン類を添加することもできる。培地のｐＨは、特に限定されないが６～８程度であるのが好ましい。 Furthermore, vitamins can be added if necessary. The pH of the medium is not particularly limited, but is preferably about 6 to 8.
　１．１．２．３．反応液
　反応液としては、炭素源、窒素源、無機塩類等を含有する天然反応液または合成反応液が用いられる。 11.2.3. Reaction solution As the reaction solution, a natural reaction solution or a synthetic reaction solution containing a carbon source, a nitrogen source, inorganic salts and the like is used.
　このうち、炭素源としては、前述した混合糖が用いられる。反応液中の混合糖の濃度は、１～２０（ｗ／ｖ％）であるのが好ましく、２～１０（ｗ／ｖ％）であるのがより好ましく、２～５（ｗ／ｖ％）であるのがさらに好ましい。 Of these, the above-mentioned mixed sugar is used as the carbon source. The concentration of the mixed sugar in the reaction solution is preferably 1 to 20 (w / v%), more preferably 2 to 10 (w / v%), and 2 to 5 (w / v%). Is more preferable.
　また、その他に、前述した炭素源から適宜選択されたものが用いられる。なお、混合糖を含む全炭素源の濃度は、２～５（ｗ／ｖ％）であるのが好ましい。 In addition, a carbon source appropriately selected from the above-mentioned carbon sources is used. The concentration of the total carbon source containing the mixed sugar is preferably 2 to 5 (w / v%).
　窒素源としては、前述した窒素源から適宜選択されたものが用いられる。反応液中の窒素源の濃度は、使用する栄養物質の濃度によっても異なるが、例えば０．０１～１（ｗ／ｖ％）とされる。 As the nitrogen source, a nitrogen source appropriately selected from the above-mentioned nitrogen sources is used. The concentration of the nitrogen source in the reaction solution varies depending on the concentration of the nutrient substance used, but is, for example, 0.01 to 1 (w / v%).
　無機塩類としては、前述した無機塩類から適宜選択されたものが用いられる。反応液中の無機塩類の濃度は、使用する栄養物質の濃度によっても異なるが、例えば０．１～１０（ｗ／ｖ％）とされる。
　さらに、必要に応じて、前述したビタミン類から適宜選択されたものが用いられる。 As the inorganic salts, those appropriately selected from the above-mentioned inorganic salts are used. The concentration of the inorganic salts in the reaction solution varies depending on the concentration of the nutritional substance used, but is, for example, 0.1 to 10 (w / v%).
Further, if necessary, those appropriately selected from the above-mentioned vitamins are used.
　１．１．２．４．反応条件
　混合糖と形質転換体との反応温度、すなわち形質転換体の生存温度は、２０～５０℃が好ましく、２５～４７℃がより好ましい。この温度範囲であれば、効率よく環式化合物を生産させることができる。 11.2.4. Reaction conditions The reaction temperature of the mixed sugar and the transformant, that is, the survival temperature of the transformant is preferably 20 to 50 ° C, more preferably 25 to 47 ° C. Within this temperature range, cyclic compounds can be efficiently produced.
　また、反応時間は、１～７日間であるのが好ましく、１～３日間であるのがより好ましい。 The reaction time is preferably 1 to 7 days, more preferably 1 to 3 days.
　培養は、バッチ式、流加式、連続式のいずれであってもよいが、特にバッチ式が好ましい。
　反応は、好気的条件で行ってもよく、還元条件で行ってもよい。 The culture may be a batch type, a fed-batch type, or a continuous type, but a batch type is particularly preferable.
The reaction may be carried out under aerobic conditions or under reducing conditions.
　還元条件にある反応液の調製方法は、公知の方法を制限なく使用できる。例えば、加熱処理や減圧処理して溶解ガスを除去することにより、還元条件の反応液用水溶液を得ることができる。この場合、好ましくは１０ｍｍＨｇ以下、より好ましくは５ｍｍＨｇ以下、さらに好ましくは３ｍｍＨｇ以下の減圧下で、好ましくは１～６０分程度、より好ましくは５～４０分程度、処理することによって、溶解ガス（特に溶解酸素）を除去し、還元条件にある反応液用水溶液を作製することができる。 As the method for preparing the reaction solution under the reduction conditions, a known method can be used without limitation. For example, an aqueous solution for a reaction solution under reducing conditions can be obtained by removing the dissolved gas by heat treatment or decompression treatment. In this case, the dissolved gas (particularly) is treated by treating with a reduced pressure of preferably 10 mmHg or less, more preferably 5 mmHg or less, still more preferably 3 mmHg or less for about 1 to 60 minutes, more preferably about 5 to 40 minutes. Dissolved oxygen) can be removed to prepare an aqueous solution for a reaction solution under reducing conditions.
　また、適当な還元剤（例えば、チオグリコール酸、アスコルビン酸、システィン塩酸塩、メルカプト酢酸、チオール酢酸、グルタチオン、硫化ソーダ等）を添加して還元条件にある反応液用水溶液を調製するようにしてもよい。
　さらに、これらの方法を適宜組み合わせるようにしてもよい。 Further, an appropriate reducing agent (for example, thioglycolic acid, ascorbic acid, cystine hydrochloride, mercaptoacetic acid, thiol acetic acid, glutathione, sodium sulfide, etc.) is added to prepare an aqueous solution for a reaction solution under the reducing conditions. May be good.
Further, these methods may be combined as appropriate.
　還元条件下で反応させる場合は、反応中も反応液を還元条件に維持することが好ましい。反応途中での還元条件を維持するために、反応系外からの酸素の混入を可能な限り防止するのが好ましい。具体的には、反応系を窒素ガス等の不活性ガスや炭酸ガス下に封入する方法が好ましく用いられる。また、反応途中において好気性細菌の菌体内の代謝機能を効率よく機能させるために、反応系のｐＨ維持調整液の添加や各種栄養素溶解液を適宜添加する必要が生じる場合もあるが、このような場合には、添加する溶液から酸素をあらかじめ除去しておくことにより、酸素混入をより効果的に防止することができる。 When reacting under reducing conditions, it is preferable to maintain the reaction solution under reducing conditions even during the reaction. In order to maintain the reduction conditions during the reaction, it is preferable to prevent the mixing of oxygen from outside the reaction system as much as possible. Specifically, a method of enclosing the reaction system under an inert gas such as nitrogen gas or carbon dioxide gas is preferably used. In addition, in order to efficiently function the metabolic function of aerobic bacteria in the cells during the reaction, it may be necessary to add a pH maintenance adjusting solution for the reaction system or various nutrient dissolving solutions as appropriate. In such a case, oxygen contamination can be more effectively prevented by removing oxygen from the solution to be added in advance.
　なお、原料液体の調製後、形質転換体を分離除去する。分離除去法としては、例えば、沈降分離法、遠心分離法、ろ過分離法等が挙げられる。また、これらのうちの複数を組み合わせた方法であってもよい。 After preparing the raw material liquid, the transformant is separated and removed. Examples of the separation / removal method include a sedimentation separation method, a centrifugation method, a filtration separation method, and the like. Further, a method in which a plurality of these are combined may be used.
　また、本工程は、必要に応じて設けられればよく、例えばリサイクル等によって生成された環式化合物を含む液体を用意する工程で置き換えられてもよい。 Further, this step may be provided as needed, and may be replaced by, for example, a step of preparing a liquid containing a cyclic compound produced by recycling or the like.
　一方、本実施形態に係る環式化合物またはその誘導体の製造方法は、上述したような、バイオマスから原料液体を調製する工程である原料液体調製工程を有している。このような工程を有することにより、環式化合物またはその誘導体の製造に際し、化石資源を消費することがないため、二酸化炭素濃度の増加を抑制することができる。このため、地球温暖化の抑制に寄与することができる。 On the other hand, the method for producing a cyclic compound or a derivative thereof according to the present embodiment includes a raw material liquid preparation step which is a step of preparing a raw material liquid from biomass as described above. By having such a step, fossil resources are not consumed in the production of the cyclic compound or its derivative, so that an increase in carbon dioxide concentration can be suppressed. Therefore, it can contribute to the suppression of global warming.
　１．１．３．濃縮処理
　なお、得られた原料液体を必要に応じて濃縮するようにしてもよい。 11.3. Concentration treatment The obtained raw material liquid may be concentrated if necessary.
　濃縮方法には、例えば、蒸留、吸着、抽出、膜分離、透析、逆浸透等が挙げられ、これらのうちの１種または２種以上が組み合わされて用いられる。 Examples of the concentration method include distillation, adsorption, extraction, membrane separation, dialysis, reverse osmosis, etc., and one or more of these are used in combination.
　このうち、本実施形態に係る濃縮処理は、加熱された伝熱面に原料液体を接触させ、原料液体に含まれる溶媒を蒸発させる処理であって、伝熱面に原料液体を繰り返し接触させる処理であるのが好ましい。このような処理によれば、原料液体に含まれる溶媒を蒸発させる際、原料液体によって伝熱面を常時濡らすことができるので、焦げの発生を抑制することができる。 Of these, the concentration treatment according to the present embodiment is a treatment in which the raw material liquid is brought into contact with the heated heat transfer surface to evaporate the solvent contained in the raw material liquid, and is a treatment in which the raw material liquid is repeatedly brought into contact with the heat transfer surface. Is preferable. According to such a treatment, when the solvent contained in the raw material liquid is evaporated, the heat transfer surface can be constantly wetted by the raw material liquid, so that the occurrence of charring can be suppressed.
　具体的には、内壁面が伝熱面になっている撹拌槽に原料液体を入れ、底部に溜まった原料液体を汲み上げる。そして、内壁面に散布しつつ原料液体を撹拌する装置を用いて原料液体を濃縮する。これにより、伝熱面の有効面積を最大限に利用することができ、濃縮効率を高めることができる。また、伝熱面が乾燥することによる焦げの発生が抑制され、最終的に回収する固体の着色を抑制することができる。 Specifically, the raw material liquid is put into a stirring tank whose inner wall surface is a heat transfer surface, and the raw material liquid accumulated at the bottom is pumped up. Then, the raw material liquid is concentrated using a device that stirs the raw material liquid while spraying it on the inner wall surface. As a result, the effective area of the heat transfer surface can be used to the maximum, and the concentration efficiency can be improved. In addition, the generation of charring due to the drying of the heat transfer surface can be suppressed, and the coloring of the finally recovered solid can be suppressed.
　濃縮処理における加熱温度は、特に限定されないが、１５～１２０℃程度であるのが好ましく、２０～９０℃程度であるのがより好ましい。これにより、焦げの発生や溶質の変性等を抑えつつ、濃縮の効率を高めることができる。 The heating temperature in the concentration treatment is not particularly limited, but is preferably about 15 to 120 ° C, more preferably about 20 to 90 ° C. As a result, the efficiency of concentration can be improved while suppressing the generation of charring and the denaturation of solutes.
　また、濃縮処理における原料溶液は、減圧下に置かれるようにしてもよい。これにより、溶媒の揮発が促進され、濃縮効率を高めることができる。原料溶液が置かれる環境の圧力は、特に限定されないが、８０ｋＰａ以下であるのが好ましく、０．１～５０ｋＰａであるのがより好ましい。 Further, the raw material solution in the concentration treatment may be placed under reduced pressure. As a result, the volatilization of the solvent is promoted, and the concentration efficiency can be increased. The pressure of the environment in which the raw material solution is placed is not particularly limited, but is preferably 80 kPa or less, and more preferably 0.1 to 50 kPa.
　なお、濃縮にあたっては、塩基性物質を用いて環式化合物の塩を調製し、水性媒体に溶解させるようにしてもよい。
　また、濃縮処理は必要に応じて行えばよく、省略されてもよい。 For concentration, a salt of the cyclic compound may be prepared using a basic substance and dissolved in an aqueous medium.
Further, the concentration treatment may be performed as needed and may be omitted.
　以上のようにして原料液体を濃縮することにより、原料液体の単位量から回収可能な固体の量の割合、すなわち収率を高めることができる。このため、後述する工程に要する時間やエネルギーを削減することができ、環式化合物の製造効率、すなわち単位時間当たりの環式化合物の生産能力を高めることができる。 By concentrating the raw material liquid as described above, the ratio of the amount of solid that can be recovered from the unit amount of the raw material liquid, that is, the yield can be increased. Therefore, the time and energy required for the steps described later can be reduced, and the production efficiency of the cyclic compound, that is, the production capacity of the cyclic compound per unit time can be increased.
　また、濃縮処理の際には、必要に応じて、減圧操作と常圧復帰操作とを繰り返すようにしてもよい。これにより、気泡の収縮と膨張とが生じ、含まれる気泡の上昇、破裂が促されるため、気泡を効率よく消滅させることができる。その結果、濃縮効率の低下を抑えることができる。 Further, during the concentration process, the depressurization operation and the normal pressure return operation may be repeated as necessary. As a result, the bubbles contract and expand, and the bubbles contained therein are promoted to rise and burst, so that the bubbles can be efficiently extinguished. As a result, a decrease in concentration efficiency can be suppressed.
　減圧操作の時間と常圧復帰操作の時間の比率は、気泡の発生の程度や濃縮速度に応じて適宜調整されるが、一例として、１：１０～１０：１程度であるのが好ましい。これにより、効率よく気泡を除去することができる。 The ratio of the depressurization operation time to the normal pressure return operation time is appropriately adjusted according to the degree of bubble generation and the concentration rate, but as an example, it is preferably about 1:10 to 10: 1. As a result, air bubbles can be efficiently removed.
　また、減圧操作の時間は、特に限定されないが、一例として１～１０秒程度であるのが好ましい。これにより、効率よく気泡を除去することができる。 The time of the depressurization operation is not particularly limited, but is preferably about 1 to 10 seconds as an example. As a result, air bubbles can be efficiently removed.
　１．２．第１乾燥工程Ｓ０２
　次に、原料液体を真空乾燥法により乾燥させ、乾燥物を得る（乾固）。具体的には、真空乾燥法では、原料液体を密閉容器に入れ、密閉容器内を減圧する。これにより、原料液体と容器内との溶媒分圧差を大きくし、乾燥を促進させる。その結果、原料液体を短時間で確実に乾燥させ、乾燥物を得ることができる。加えて、低分子の不純物成分を効率よく除去することができるので、最終的に得られる環式化合物の純度や白色度を高めることができる。 1.2. First drying step S02
Next, the raw material liquid is dried by a vacuum drying method to obtain a dried product (dry solid). Specifically, in the vacuum drying method, the raw material liquid is placed in a closed container and the inside of the closed container is depressurized. As a result, the difference in solvent partial pressure between the raw material liquid and the inside of the container is increased, and drying is promoted. As a result, the raw material liquid can be reliably dried in a short time to obtain a dried product. In addition, since small molecule impurity components can be efficiently removed, the purity and whiteness of the finally obtained cyclic compound can be increased.
　また、真空乾燥法では、減圧下で処理されることから酸化や燃焼等が生じにくい。このため、環式化合物の酸化等の変性や焦げ付きによる着色等が抑制される。その結果、最終的に得られる環式化合物の純度や白色度を高めることができる。 Also, in the vacuum drying method, oxidation and combustion are unlikely to occur because the treatment is performed under reduced pressure. Therefore, denaturation such as oxidation of the cyclic compound and coloring due to scorching are suppressed. As a result, the purity and whiteness of the finally obtained cyclic compound can be increased.
　本実施形態に係る真空乾燥法による乾燥処理は、圧力１０Ｐａ以下において温度６５～１２５℃で加熱する処理である。このような条件で加熱することにより、環式化合物の酸化等の編成や着色等を抑制しつつ、低分子の不純物成分をより効率よく除去することができる。その結果、最終的に得られる環式化合物の純度や白色度を高めることができる。また、このような加熱条件によれば、環式化合物の減少を抑えることができるので、最終的に得られる環式化合物の収率も高めることができる。 The drying process by the vacuum drying method according to the present embodiment is a process of heating at a temperature of 65 to 125 ° C. at a pressure of 10 Pa or less. By heating under such conditions, it is possible to more efficiently remove low-molecular-weight impurity components while suppressing the formation and coloring of the cyclic compound such as oxidation. As a result, the purity and whiteness of the finally obtained cyclic compound can be increased. Further, according to such heating conditions, the decrease of the cyclic compound can be suppressed, so that the yield of the finally obtained cyclic compound can be increased.
　なお、乾燥処理における圧力は、好ましくは５．０Ｐａ以下とされ、経済性も考慮すると、より好ましくは１．０×１０－６Ｐａ以上１．０Ｐａ以下とされる。 The pressure in the drying treatment is preferably 5.0 Pa or less, and more preferably 1.0 × 10 -6 Pa or more and 1.0 Pa or less in consideration of economic efficiency.
　圧力が前記上限値を上回ると、環式化合物の純度が低下するおそれがある。一方、圧力が前記下限値を下回ってもよいが、効果のさらなる上積みは期待できない。 If the pressure exceeds the upper limit, the purity of the cyclic compound may decrease. On the other hand, the pressure may be lower than the lower limit, but no further increase in the effect can be expected.
　また、乾燥処理における温度は、好ましくは６０～１２０℃とされ、より好ましくは９０～１１０℃とされる。これにより、収率を低下させることなく、低分子の不純物成分を特に効率よく除去することができる。 The temperature in the drying treatment is preferably 60 to 120 ° C, more preferably 90 to 110 ° C. This makes it possible to remove small molecule impurity components particularly efficiently without lowering the yield.
　温度が前記上限値を上回ると、環式化合物が変性してしまい、純度および収率が低下するおそれがある。一方、温度が前記下限値を下回ると、純度が低下したり、乾燥時間が長時間になるおそれがある。 If the temperature exceeds the upper limit, the cyclic compound may be denatured and the purity and yield may decrease. On the other hand, if the temperature is lower than the lower limit, the purity may decrease or the drying time may become long.
　加熱時間は、溶媒の蒸発の進行度合いに応じて適宜設定されるが、一例として１０分～２４時間程度であるのが好ましく、３０分～６時間程度であるのがより好ましい。 The heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 24 hours, and more preferably about 30 minutes to 6 hours.
　真空乾燥法による乾燥処理では、前述した密閉容器と真空ポンプとを備えた真空乾燥機を用いることができる。 In the drying process by the vacuum drying method, a vacuum dryer equipped with the above-mentioned closed container and vacuum pump can be used.
　なお、本工程では全ての溶媒を除去する必要はなく、一部の溶媒を残存させるようにしてもよい。つまり、第１乾燥工程は、不完全な乾燥物を得る工程であってもよい。 It should be noted that it is not necessary to remove all the solvents in this step, and some solvents may remain. That is, the first drying step may be a step of obtaining an incompletely dried product.
　また、得られた乾燥物は、必要に応じて、解砕または粉砕されるようにしてもよい。これにより、乾燥物の比表面積が大きくなるため、後述する再溶解工程において環式化合物の溶解効率を高めることができる。 Further, the obtained dried product may be crushed or crushed as needed. As a result, the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the redissolution step described later.
　１．３．再溶解工程Ｓ０３
　次に、得られた乾燥物を再溶解用溶媒に溶解し、溶液（再溶解液）を調製する。溶液を調製することにより、後述する吸着工程が可能になる。 1.3. Redissolution step S03
Next, the obtained dried product is dissolved in a redissolving solvent to prepare a solution (resolving solution). By preparing the solution, the adsorption step described later becomes possible.
　再溶解用溶媒には、乾燥物を溶解させる良溶媒が用いられる。良溶媒としては、例えば、水、メタノール、ヘキサン、クロロホルム等が挙げられる。 As the redissolving solvent, a good solvent that dissolves the dried product is used. Examples of the good solvent include water, methanol, hexane, chloroform and the like.
　１．４．吸着工程Ｓ０４
　次に、溶液に対して吸着処理を施すが、それに先立って、溶液に含まれる環式化合物をイオン化させる処理を施すようにしてもよい。この処理は、環式化合物のイオン化傾向を利用して、溶液の条件を変更することにより、イオン化率を高める処理である。このような処理を施すことにより、溶液中の環式化合物の存在比率を低下させることができる。本実施形態では、吸着処理に供する溶液（第１溶液）の調製に際し、溶液における環式化合物の存在量が、環式化合物のイオンの存在量よりも少なくなるように、溶液を調製する。その結果、その後の吸着処理において、環式化合物が吸着媒体に吸着されてしまい、最終的な環式化合物の収率が低下するのを抑制することができる。 1.4. Adsorption step S04
Next, the solution is subjected to an adsorption treatment, but prior to that, a treatment for ionizing the cyclic compound contained in the solution may be performed. This treatment is a treatment for increasing the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be reduced. In the present embodiment, when preparing the solution (first solution) to be subjected to the adsorption treatment, the solution is prepared so that the abundance of the cyclic compound in the solution is smaller than the abundance of ions of the cyclic compound. As a result, in the subsequent adsorption treatment, it is possible to prevent the cyclic compound from being adsorbed on the adsorption medium and reduce the yield of the final cyclic compound.
　変更する溶液の条件としては、例えば、溶液のｐＨ、溶液の温度等が挙げられる。このうち、溶液のｐＨを変更する場合、例えば溶液に酸またはアルカリを添加する。アルカリを添加すると、ｐＨを上昇させることができる。これにより、溶液における環式化合物のイオン化率を高めることができる。一方、酸を添加すると、ｐＨを低下させることができる。これにより、溶液における環式化合物のイオン化率が低下し、反対に、環式化合物の存在比率が高くなる。 The conditions of the solution to be changed include, for example, the pH of the solution, the temperature of the solution, and the like. Of these, when changing the pH of the solution, for example, an acid or an alkali is added to the solution. The pH can be increased by adding alkali. This makes it possible to increase the ionization rate of the cyclic compound in the solution. On the other hand, the addition of acid can lower the pH. As a result, the ionization rate of the cyclic compound in the solution decreases, and conversely, the abundance ratio of the cyclic compound increases.
　アルカリを添加する場合、アルカリ添加後の溶液のｐＨは、５．０～７．５程度であるのが好ましく、５．５～６．５程度であるのがより好ましい。これにより、溶液における環式化合物の存在比率を低下させることができる。その結果、後述する吸着処理において、環式化合物が吸着媒体に吸着される確率を低下させることができる。
　アルカリとしては、例えば、水酸化ナトリウム、水酸化カリウム等が挙げられる。 When the alkali is added, the pH of the solution after the addition of the alkali is preferably about 5.0 to 7.5, and more preferably about 5.5 to 6.5. This makes it possible to reduce the abundance ratio of the cyclic compound in the solution. As a result, the probability that the cyclic compound is adsorbed on the adsorption medium can be reduced in the adsorption treatment described later.
Examples of the alkali include sodium hydroxide, potassium hydroxide and the like.
　また、酸としては、例えば、ギ酸、酢酸、塩酸、プロピオン酸、酪酸、吉草酸等が挙げられる。 Examples of the acid include formic acid, acetic acid, hydrochloric acid, propionic acid, butyric acid, valeric acid and the like.
　次に、溶液に対して吸着処理を施す。吸着処理は、溶液に吸着媒体を接触させ、溶液中の高分子成分等を吸着媒体に吸着させる処理である。これにより、溶液中の不純物、例えば高分子の有機成分等が除去される。その結果、最終的に得られる環式化合物の純度を高めるとともに、着色を抑制することができる。なお、吸着処理において吸着、除去するのは、高分子の有機成分に限定されず、いかなる不純物であってもよい。 Next, the solution is adsorbed. The adsorption treatment is a treatment in which the adsorption medium is brought into contact with the solution and the polymer components and the like in the solution are adsorbed on the adsorption medium. As a result, impurities in the solution, for example, organic components of the polymer are removed. As a result, the purity of the finally obtained cyclic compound can be increased and coloring can be suppressed. It should be noted that what is adsorbed and removed in the adsorption treatment is not limited to the organic component of the polymer, and any impurity may be used.
　吸着媒体は、吸着能を有する媒体であれば、特に限定されないが、例えば活性炭、シリカゲル、ゼオライト等である。そして、吸着処理では、溶液に吸着媒体を接触させることができれば、いかなる方法も用いられる。 The adsorption medium is not particularly limited as long as it has an adsorptive ability, but is, for example, activated carbon, silica gel, zeolite, or the like. Then, in the adsorption treatment, any method is used as long as the adsorption medium can be brought into contact with the solution.
　吸着処理における溶液の温度は、例えば３０～１５０℃程度とされる。また、吸着処理の時間は、特に限定されないが、１０分～１０時間程度であるのが好ましい。 The temperature of the solution in the adsorption treatment is, for example, about 30 to 150 ° C. The time of the adsorption treatment is not particularly limited, but is preferably about 10 minutes to 10 hours.
　また、吸着媒体として活性炭を用いる場合、溶液１００ｇに対する活性炭の添加量は、特に限定されないが、０．０１～３．０ｇであるのが好ましく、０．１～１．０ｇであるのがより好ましい。これにより、不純物を高い確率で吸着し、最終的な環式化合物の純度を高めるとともに、着色を抑制することができる。 When activated carbon is used as the adsorption medium, the amount of activated carbon added to 100 g of the solution is not particularly limited, but is preferably 0.01 to 3.0 g, more preferably 0.1 to 1.0 g. .. As a result, impurities can be adsorbed with a high probability, the purity of the final cyclic compound can be increased, and coloring can be suppressed.
　なお、本工程は、必要に応じて行えばよく、省略されてもよい。その場合、吸着工程と併せて、再溶解工程および第２乾燥工程を省略してもよい。また、吸着工程の順序は、本実施形態に限定されず、例えば第１乾燥工程の前であってもよく、抽出工程と析出工程との間であってもよい。
　また、吸着処理後の吸着媒体は、ろ過等の固液分離処理によって除去される。 It should be noted that this step may be performed as needed or may be omitted. In that case, the redissolving step and the second drying step may be omitted in addition to the adsorption step. Further, the order of the adsorption steps is not limited to this embodiment, and may be, for example, before the first drying step or between the extraction step and the precipitation step.
Further, the adsorption medium after the adsorption treatment is removed by a solid-liquid separation treatment such as filtration.
　１．５．第２乾燥工程Ｓ０５
　次に、吸着工程を経た溶液を乾燥させ、乾燥物を得るが、それに先立って、溶液に含まれる環式化合物のイオンを非イオン化させる処理を施すようにしてもよい。この処理は、環式化合物のイオン化傾向を利用して、溶液の条件を変更することにより、イオン化率を下げる処理である。このような処理を施すことにより、溶液中の環式化合物の存在比率を高めることができる。本実施形態では、乾燥処理に供する溶液（第２溶液）の調製に際し、吸着工程を経た溶液における環式化合物の存在量が、環式化合物のイオンの存在量よりも少なくなるように、溶液を調製する。その結果、本工程の後の抽出工程において、環式化合物の収率を高めることができる。 1.5. Second drying step S05
Next, the solution that has undergone the adsorption step is dried to obtain a dried product, but prior to that, a treatment for deionizing the ions of the cyclic compound contained in the solution may be performed. This treatment is a treatment for lowering the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be increased. In the present embodiment, when preparing the solution (second solution) to be subjected to the drying treatment, the solution is prepared so that the abundance of the cyclic compound in the solution that has undergone the adsorption step is smaller than the abundance of ions of the cyclic compound. Prepare. As a result, the yield of the cyclic compound can be increased in the extraction step after this step.
　イオン化率を下げる処理としては、例えば、酸を添加する処理が挙げられる。酸添加後の溶液のｐＨは、２．０～４．５程度であるのが好ましく、２．５～３．５程度であるのがより好ましい。これにより、溶液における環式化合物の存在比率を高めることができる。その結果、後述する抽出工程において、環式化合物の収率を高めることができる。 Examples of the treatment for lowering the ionization rate include a treatment for adding an acid. The pH of the solution after the addition of the acid is preferably about 2.0 to 4.5, more preferably about 2.5 to 3.5. This makes it possible to increase the abundance ratio of the cyclic compound in the solution. As a result, the yield of the cyclic compound can be increased in the extraction step described later.
　また、乾燥物を得るのに先立ち、イオン化率を下げる処理とは別に、またはそれとともに、濃縮処理を施すようにしてもよい。これにより、乾燥に要する時間を短縮するとともに、必要なエネルギーを削減することができる。この濃縮処理は、前述した条件で行うことができる。 Further, prior to obtaining the dried product, a concentration treatment may be performed separately from or in combination with the treatment for lowering the ionization rate. As a result, the time required for drying can be shortened and the required energy can be reduced. This concentration treatment can be performed under the conditions described above.
　以上のような処理を経た後、吸着工程を経た溶液を乾燥させる。第２乾燥工程における乾燥方法としては、例えば、煮沸乾燥法、噴霧乾燥法、伝熱乾燥法、赤外線乾燥法、温風乾燥法、真空乾燥法等が挙げられる。また、これらの乾燥法を含む複数種の乾燥法を組み合わせて適用するようにしてもよい。第２乾燥工程では、前述した第１乾燥工程と同様の方法、つまり真空乾燥法を用いるようにしてもよいが、異なる方法を用いるようにしてもよい。以下、真空乾燥法以外の代表的な３つの乾燥法について順次説明する。 After undergoing the above treatment, the solution that has undergone the adsorption step is dried. Examples of the drying method in the second drying step include a boiling drying method, a spray drying method, a heat transfer drying method, an infrared drying method, a warm air drying method, and a vacuum drying method. Further, a plurality of types of drying methods including these drying methods may be applied in combination. In the second drying step, the same method as the first drying step described above, that is, the vacuum drying method may be used, but a different method may be used. Hereinafter, three typical drying methods other than the vacuum drying method will be sequentially described.
　１．５．１．煮沸乾燥法
　煮沸乾燥法（煮沸乾固法）では、例えばホットプレート等の加熱装置を用い、容器に入れた原料液体を加熱する。熱伝導で容器が加熱されると、原料液体中の溶媒が蒸発する。溶媒の蒸発が進むと、固体が乾燥し、乾燥物が得られる。このような煮沸乾燥法によれば、簡易的な装置を用いることができるので、製造コストの削減を図りやすいという利点がある。 1.5.1. Boil-drying method In the boiling-drying method (boil-drying method), for example, a heating device such as a hot plate is used to heat the raw material liquid contained in the container. When the container is heated by heat conduction, the solvent in the raw material liquid evaporates. As the solvent evaporates, the solid dries and a dried product is obtained. According to such a boiling and drying method, since a simple device can be used, there is an advantage that the manufacturing cost can be easily reduced.
　加熱温度は、溶媒が気化する温度以上に設定すればよいので、溶媒の種類に応じて異なる。一例として、７０～２００℃程度であるのが好ましく、８０～１５０℃程度であるのがより好ましい。これにより、環式化合物の変性や分解、着色等を抑制しつつ、溶媒を効率よく蒸発させることができる。 The heating temperature may be set above the temperature at which the solvent evaporates, so it differs depending on the type of solvent. As an example, the temperature is preferably about 70 to 200 ° C, more preferably about 80 to 150 ° C. As a result, the solvent can be efficiently evaporated while suppressing denaturation, decomposition, coloring and the like of the cyclic compound.
　加熱時間は、溶媒の蒸発の進行度合いに応じて適宜設定されるが、一例として１０分～１０時間程度であるのが好ましく、３０分～６時間程度であるのがより好ましい。 The heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 10 hours, and more preferably about 30 minutes to 6 hours.
　なお、加熱に伴う酸化を抑制するため、必要に応じて、非酸化性ガス下で加熱したり、非酸化性ガスを吹き付けながら加熱したりするようにしてもよい。 Note that, in order to suppress oxidation due to heating, heating may be performed under a non-oxidizing gas, or heating may be performed while blowing a non-oxidizing gas, if necessary.
　また、得られた乾燥物は、必要に応じて、解砕または粉砕されるようにしてもよい。これにより、乾燥物の比表面積が大きくなるため、後述する再溶解工程において環式化合物の溶解効率を高めることができる。 Further, the obtained dried product may be crushed or crushed as needed. As a result, the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the redissolution step described later.
　１．５．２．噴霧乾燥法
　噴霧乾燥法（スプレードライ法）は、例えば原料液体を乾燥室内のノズルで微粒化し、温風に接触させる（噴霧乾燥する）方法である。これにより、原料液体中の溶媒が蒸発するとともに、析出した溶質が粒子状に成形される。このため、取り扱いが容易な乾燥物が得られる。 1.5.2. Spray drying method The spray drying method (spray drying method) is, for example, a method in which a raw material liquid is atomized by a nozzle in a drying chamber and brought into contact with warm air (spray drying). As a result, the solvent in the raw material liquid evaporates, and the precipitated solute is formed into particles. Therefore, a dried product that is easy to handle can be obtained.
　また、乾燥に先立って原料液体を微粒化することから、原料液体の比表面積が大きくなる。このため、短時間で均一な昇温が可能になり、溶質の変性や分解等を最小限に留めることができる。加えて、かかる乾燥物は後述する再溶解工程において環式化合物の溶解効率が高いものとなる。 In addition, since the raw material liquid is atomized prior to drying, the specific surface area of the raw material liquid becomes large. Therefore, it is possible to raise the temperature uniformly in a short time, and it is possible to minimize the denaturation and decomposition of the solute. In addition, the dried product has a high dissolution efficiency of the cyclic compound in the redissolution step described later.
　さらに、原料液体に対する熱伝導が温風を介したものであるため、昇温ムラが少なく、乾燥状態の均一化を図りやすいという利点もある。
　また、原料液体の昇温効率が高く、エネルギー効率が高いという利点もある。 Further, since the heat conduction to the raw material liquid is via warm air, there is an advantage that there is little unevenness in temperature rise and it is easy to make the dry state uniform.
It also has the advantages of high heating efficiency of the raw material liquid and high energy efficiency.
　なお、噴霧乾燥法で得られた乾燥物は、比較的粒径が揃った粒子となる。このため、その後の分級処理を省略したり、簡素化したりすることができ、製造コストを抑えつつ、流動性が高くて扱いやすい乾燥物を得ることができる。 The dried product obtained by the spray drying method has particles having a relatively uniform particle size. Therefore, the subsequent classification process can be omitted or simplified, and a dried product having high fluidity and easy handling can be obtained while suppressing the manufacturing cost.
　製造される粒子状の乾燥物の平均粒径は、特に限定されないが、５～３００μｍ程度であるのが好ましく、１０～２００μｍ程度であるのがより好ましい。これにより、後述する工程において処理効率が高く、かつ、流動性等の観点から扱いやすい乾燥物が得られる。 The average particle size of the produced particulate dried product is not particularly limited, but is preferably about 5 to 300 μm, and more preferably about 10 to 200 μm. As a result, a dried product having high treatment efficiency in the steps described later and easy to handle from the viewpoint of fluidity and the like can be obtained.
　また、温風の入口温度は、溶媒の沸点に応じて適宜設定されるが、一例として３０～２００℃程度であるのが好ましく、４０～１５０℃程度であるのがより好ましい。 The inlet temperature of the warm air is appropriately set according to the boiling point of the solvent, but as an example, it is preferably about 30 to 200 ° C, more preferably about 40 to 150 ° C.
　さらに、噴霧乾燥法では、閉空間で乾燥させることができるので、必要に応じて、窒素やアルゴンのような不活性ガス下で乾燥させることができる。これにより、乾燥物の酸化を抑制することができる。 Furthermore, in the spray drying method, since it can be dried in a closed space, it can be dried under an inert gas such as nitrogen or argon, if necessary. This makes it possible to suppress the oxidation of the dried product.
　１．５．３．伝熱乾燥法
　伝熱乾燥法（間接加熱乾燥法）は、例えば伝熱面を介して原料液体を間接的に加熱する方法である。これにより、伝熱面に接触した原料液体中の溶媒が蒸発し、乾燥物が得られる。 1.5.3. Heat transfer drying method The heat transfer drying method (indirect heat transfer drying method) is a method of indirectly heating the raw material liquid through, for example, a heat transfer surface. As a result, the solvent in the raw material liquid in contact with the heat transfer surface evaporates, and a dried product is obtained.
　伝熱面としては、例えばディスク、ドラム、シリンダー等の形状をした金属体が挙げられる。伝熱乾燥法では、これらの伝熱面に原料液体が散布されると、短時間で乾燥し、伝熱面上に乾燥物が得られる。この乾燥物は、スクレーパー等でかき落され、塊状物または粒状物として回収される。 Examples of the heat transfer surface include metal bodies in the shape of discs, drums, cylinders, and the like. In the heat transfer drying method, when the raw material liquid is sprayed on these heat transfer surfaces, it dries in a short time, and a dried product is obtained on the heat transfer surfaces. This dried product is scraped off with a scraper or the like and collected as a lump or a granular material.
　また、乾燥に先立って原料液体を薄膜化することから、原料液体の比表面積が大きくなる。このため、短時間で均一な昇温が可能になり、溶質の変性や分解等を最小限に留めることができる。 In addition, since the raw material liquid is thinned prior to drying, the specific surface area of the raw material liquid becomes large. Therefore, it is possible to raise the temperature uniformly in a short time, and it is possible to minimize the denaturation and decomposition of the solute.
　なお、伝熱面の温度は、溶媒の沸点に応じて適宜設定されるが、例えば７０～２００℃程度であるのが好ましく、８０～１５０℃程度であるのがより好ましい。これにより、環式化合物の変性や分解、着色等を抑制しつつ、溶媒を効率よく蒸発させることができる。 The temperature of the heat transfer surface is appropriately set according to the boiling point of the solvent, but is preferably about 70 to 200 ° C., more preferably about 80 to 150 ° C., for example. As a result, the solvent can be efficiently evaporated while suppressing denaturation, decomposition, coloring and the like of the cyclic compound.
　また、伝熱面を減圧下に置くようにしてもよい。これにより、溶媒の蒸発効率を高めるとともに、環式化合物の酸化や焦げ付き等を抑制することができる。 Alternatively, the heat transfer surface may be placed under reduced pressure. This makes it possible to increase the evaporation efficiency of the solvent and suppress oxidation and scorching of the cyclic compound.
　加熱時間は、溶媒の蒸発の進行度合いに応じて適宜設定されるが、一例として１０分～１０時間程度であるのが好ましく、３０分～６時間程度であるのがより好ましい。 The heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 10 hours, and more preferably about 30 minutes to 6 hours.
　なお、得られた乾燥物は、必要に応じて、解砕または粉砕されるようにしてもよい。これにより、乾燥物の比表面積が大きくなるため、後述する抽出工程において環式化合物の溶解効率を高めることができる。 The obtained dried product may be crushed or crushed as needed. As a result, the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the extraction step described later.
　以上、３つの乾燥法について説明したが、本工程では全ての溶媒を除去する必要はなく、一部の溶媒を残存させるようにしてもよい。つまり、第２乾燥工程は、不完全な乾燥物を得る工程であってもよい。 Although the three drying methods have been described above, it is not necessary to remove all the solvents in this step, and some solvents may remain. That is, the second drying step may be a step of obtaining an incompletely dried product.
　乾燥物における溶媒の含有率は、３０質量％以下であるのが好ましく、１質量％以上２０質量％以下であるのがより好ましい。これにより、最終的な乾燥に要する時間やエネルギーが抑えられるため、効率のよい処理が可能になる。 The content of the solvent in the dried product is preferably 30% by mass or less, and more preferably 1% by mass or more and 20% by mass or less. As a result, the time and energy required for final drying can be reduced, so that efficient processing becomes possible.
　そして、以上のような第２乾燥工程においても、溶媒の揮発に伴って主に低分子の有機成分を除去することができる。これにより、最終的に得られる環式化合物の純度をより高めることができる。 And, even in the second drying step as described above, mainly small molecule organic components can be removed as the solvent volatilizes. Thereby, the purity of the finally obtained cyclic compound can be further increased.
　なお、後に説明するが、後述する抽出工程において、固液抽出処理ではなく、液液抽出処理を採用した場合には、本工程を省略することができる。 As will be described later, if a liquid-liquid extraction process is adopted instead of the solid-liquid extraction process in the extraction step described later, this step can be omitted.
　１．６．抽出工程Ｓ０６
　次に、固液抽出用の溶媒（抽出用溶媒）により、乾燥物に固液抽出処理を施し、抽出液を得る。 1.6. Extraction step S06
Next, the dried product is subjected to a solid-liquid extraction treatment with a solvent for solid-liquid extraction (extraction solvent) to obtain an extract.
　固液抽出処理は、乾燥物中に含まれている環式化合物について、固液抽出用の溶媒に対する溶解性を利用して選択的に抽出する処理である。すなわち、環式化合物を溶解させる溶媒側に環式化合物を選択的に移行させ、無機塩等の不純物については乾燥物中に残存させることができる。その結果、抽出液に含まれる環式化合物の純度を高めることができる。 The solid-liquid extraction process is a process for selectively extracting a cyclic compound contained in a dried product by utilizing its solubility in a solvent for solid-liquid extraction. That is, the cyclic compound can be selectively transferred to the solvent side where the cyclic compound is dissolved, and impurities such as inorganic salts can be left in the dried product. As a result, the purity of the cyclic compound contained in the extract can be increased.
　固液抽出用の溶媒としては、例えば、水、メタノール、エタノール、イソプロパノール、アセトン、アセトニトリル、ヘキサン、クロロホルム、テトラヒドロフラン等が挙げられる。 Examples of the solvent for solid-liquid extraction include water, methanol, ethanol, isopropanol, acetone, acetonitrile, hexane, chloroform, tetrahydrofuran and the like.
　固液抽出処理の温度は、特に限定されないが、５～８０℃程度であるのが好ましく、１０～５０℃程度であるのがより好ましい。これにより、溶液の溶解度を最適化することができるので、抽出される環式化合物の純度と、抽出率（抽出能力）と、を両立させることができる。 The temperature of the solid-liquid extraction treatment is not particularly limited, but is preferably about 5 to 80 ° C, more preferably about 10 to 50 ° C. As a result, the solubility of the solution can be optimized, so that the purity of the cyclic compound to be extracted and the extraction rate (extraction ability) can be compatible with each other.
　なお、温度が前記下限値未満である場合、抽出率が低下するおそれがある。一方、温度が前記上限値を上回ると、不純物も移行しやすくなり、環式化合物の純度が低下するおそれがある。 If the temperature is less than the lower limit, the extraction rate may decrease. On the other hand, when the temperature exceeds the upper limit value, impurities are likely to migrate, and the purity of the cyclic compound may decrease.
　また、固液抽出処理の時間は、温度に応じて適宜設定されるが、例えば３０分～１０時間程度とされる。
　なお、加圧下において加熱することにより、抽出率を高めることもできる。 The time of the solid-liquid extraction process is appropriately set according to the temperature, and is, for example, about 30 minutes to 10 hours.
The extraction rate can also be increased by heating under pressure.
　また、固液抽出用の溶媒の量は、特に限定されないが、乾燥物１ｇに対して３～２００ｇ程度であるのが好ましく、１０～５０ｇ程度であるのがより好ましい。これにより、溶媒の量が最適化される。すなわち、溶媒の量が前記下限値を下回ると、抽出物の溶解が飽和して、抽出しきれないおそれがある。一方、溶媒の量が前記上限値を上回ると、余剰の溶媒が生じて、無駄になるおそれがある。また、不純物の抽出量が多くなり、環式化合物の純度が低下するおそれがある。 The amount of the solvent for solid-liquid extraction is not particularly limited, but is preferably about 3 to 200 g per 1 g of the dried product, and more preferably about 10 to 50 g. This optimizes the amount of solvent. That is, if the amount of the solvent is less than the lower limit, the dissolution of the extract may be saturated and the extract may not be completely extracted. On the other hand, if the amount of the solvent exceeds the upper limit value, excess solvent may be generated and wasted. In addition, the amount of impurities extracted may increase, and the purity of the cyclic compound may decrease.
　一方、吸着工程を経た後の溶液に対し、第２乾燥工程を省略するとともに、固液抽出処理に代えて液液抽出処理を施すようにしてもよい。液液抽出処理は、液液抽出用の溶媒に対する溶解性の違いを利用して、溶液中に含まれている環式化合物およびそれ以外の不純物から、環式化合物を選択的に抽出する処理である。これにより、液液抽出用の溶媒側に環式化合物を選択的に移行させることができる。その結果、より純度の高い環式化合物の取り出しが可能になる。 On the other hand, the solution after the adsorption step may be subjected to a liquid-liquid extraction treatment instead of the solid-liquid extraction treatment while omitting the second drying step. The liquid-liquid extraction process is a process for selectively extracting a cyclic compound from a cyclic compound and other impurities contained in the solution by utilizing the difference in solubility in a solvent for liquid-liquid extraction. be. As a result, the cyclic compound can be selectively transferred to the solvent side for liquid-liquid extraction. As a result, it becomes possible to take out a cyclic compound having a higher purity.
　液液抽出用の溶媒としては、例えば、ｎ－ブタノール、イソブタノール、イソ－ｎ－ペンタノール、イソペンチルアルコール、ｎ－ヘキサノール、２－ヘキサノール、クロロホルム、ヘキサン、ジエチルエーテル、ジクロロメタン、四塩化炭素等が挙げられる。 Examples of the solvent for liquid-liquid extraction include n-butanol, isobutanol, iso-n-pentanol, isopentyl alcohol, n-hexanol, 2-hexanol, chloroform, hexane, diethyl ether, dichloromethane, carbon tetrachloride and the like. Can be mentioned.
　１．７．析出工程Ｓ０７
　次に、抽出液に析出処理を施し、抽出液の溶質を固体として析出させる。この析出処理は、抽出液中の溶媒を除去可能な処理であれば、いかなる処理であってもよい。
　かかる析出処理の具体例としては、濃縮乾固、晶析等が挙げられる。 1.7. Precipitation step S07
Next, the extract is subjected to a precipitation treatment to precipitate the solute of the extract as a solid. This precipitation treatment may be any treatment as long as the solvent in the extract can be removed.
Specific examples of such a precipitation treatment include concentrated dryness, crystallization and the like.
　１．７．１．濃縮乾固
　このうち、濃縮乾固は、抽出液に含まれる溶媒を蒸発させることにより、溶質を取り出す処理である。このような処理によれば、加熱または減圧のような簡単な操作で、抽出液から環式化合物の固体を容易に取り出すことができる。また、溶質の取り出しと乾燥とを同時に行うことができるので、高効率の処理が可能になる。 1.7.1. Concentrated dry solid Of these, concentrated dry solid is a process for extracting solutes by evaporating the solvent contained in the extract. According to such a treatment, the solid of the cyclic compound can be easily taken out from the extract by a simple operation such as heating or depressurizing. Moreover, since the solute can be taken out and dried at the same time, highly efficient processing becomes possible.
　このような濃縮乾固処理には、例えば加熱方式、減圧方式、ガス吹付方式等が挙げられ、これらのうちの１種または複数方式を組み合わせた方法を用いる。 Examples of such a concentrated dry-solid treatment include a heating method, a decompression method, a gas spraying method, and the like, and one or a combination of these methods is used.
　このうち、抽出液を加熱して溶媒を揮発させる方式が好ましく用いられる。加熱温度は、溶媒を揮発させ得る温度であり、かつ、環式化合物の融点を下回る温度であれば、特に限定されないが、例えば５０～３００℃程度であるのが好ましく、８０～２５０℃程度であるのがより好ましい。これにより、環式化合物の変質を抑制しつつ、溶媒を効率よく除去することができる。 Of these, the method of heating the extract to volatilize the solvent is preferably used. The heating temperature is not particularly limited as long as it is a temperature at which the solvent can be volatilized and is lower than the melting point of the cyclic compound, but is preferably about 50 to 300 ° C., preferably about 80 to 250 ° C. It is more preferable to have it. As a result, the solvent can be efficiently removed while suppressing the alteration of the cyclic compound.
　１．７．２．晶析
　一方、晶析は、抽出液における溶質の溶解度を下げることによって溶質を析出させる処理である。このような処理によれば、純度の高い環式化合物を高い収率で取り出すことができる。 1.7.2. Crystallization On the other hand, crystallization is a process of precipitating a solute by lowering the solubility of the solute in the extract. According to such a treatment, a highly pure cyclic compound can be taken out in a high yield.
　抽出液における溶質の溶解度を低下させる処理としては、抽出液の温度を変化させ溶解度の温度依存性を利用して晶析する処理、加熱または減圧等の操作により抽出液から溶媒を揮発除去し晶析する処理、溶質の溶解度が低い溶媒を添加し溶解度の溶媒種依存性を利用して晶析する処理、抽出液のｐＨを変化させ溶解度のｐＨ応答性を利用して晶析する処理等が挙げられ、これらのうちの１種または複数種を組み合わせて用いられる。 As a treatment for lowering the solubility of the solute in the extract, the solvent is volatilized and removed from the extract by a treatment of changing the temperature of the extract and crystallization utilizing the temperature dependence of the solubility, heating or depressurization, and crystals. The treatment of crystallization, the treatment of adding a solvent with low solubility of the solute and crystallization using the solvent type dependence of the solubility, the treatment of changing the pH of the extract and crystallization using the pH responsiveness of the solubility, etc. These are mentioned, and one or more of these are used in combination.
　このうち、抽出液の温度を操作する方法が好ましく用いられる。抽出液の温度は比較的容易に操作することができるので、抽出液の温度を操作する方法は、作業性が高いという観点で有用である。 Of these, the method of manipulating the temperature of the extract is preferably used. Since the temperature of the extract can be manipulated relatively easily, the method of manipulating the temperature of the extract is useful from the viewpoint of high workability.
　晶析処理において操作される温度範囲は、環式化合物の組成や溶媒の種類等に応じて異なり、特に限定されないが、例えば５～８０℃程度であるのが好ましく、１０～７０℃程度であるのがより好ましい。これにより、取り出される環式化合物の純度と収率とを両立させることができる。 The temperature range operated in the crystallization treatment varies depending on the composition of the cyclic compound, the type of solvent, and the like, and is not particularly limited, but is preferably about 5 to 80 ° C., for example, about 10 to 70 ° C. Is more preferable. This makes it possible to achieve both the purity and the yield of the cyclic compound to be taken out.
　なお、晶析処理は、バッチ処理であっても連続処理であってもよい。また、晶析処理には、例えば公知の撹拌槽を用いることができる。 The crystallization treatment may be a batch treatment or a continuous treatment. Further, for the crystallization treatment, for example, a known stirring tank can be used.
　また、抽出液の温度を操作する方法は、特に、原料液体である抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を１回ずつ行う操作または複数回繰り返す操作を含むのが好ましい。これにより、最終的に高純度な環式化合物を高い収率で回収することができる。なお、複数回とは、特に３回以上であるのが好ましい。 Further, the method of manipulating the temperature of the extract includes, in particular, an operation of lowering the temperature of the extract as a raw material liquid and an operation of stirring the extract, one operation at a time or an operation of repeating the operation a plurality of times. Is preferable. As a result, a high-purity cyclic compound can be finally recovered in a high yield. The plurality of times is particularly preferably 3 times or more.
　温度を低下させる操作における低下幅は、特に限定されず、操作の回数に応じて適宜選択される。一例としては、１．０℃以上５０℃以下であるのが好ましく、５．０℃以上３０℃以下であるのがより好ましい。 The amount of decrease in the operation of lowering the temperature is not particularly limited, and is appropriately selected according to the number of operations. As an example, it is preferably 1.0 ° C. or higher and 50 ° C. or lower, and more preferably 5.0 ° C. or higher and 30 ° C. or lower.
　また、温度を低下させる操作における低下速度は、特に限定されないが、０．１℃／分以上５．０℃／分以下程度であるのが好ましい。これにより、不純物の巻き込みを抑えつつ、かつ、効率よく環式化合物を析出させることができるので、最終的に高純度の環式化合物が生産性よく得られる。 The rate of decrease in the operation of lowering the temperature is not particularly limited, but is preferably about 0.1 ° C./min or more and 5.0 ° C./min or less. As a result, the cyclic compound can be efficiently precipitated while suppressing the entrainment of impurities, so that a high-purity cyclic compound can be finally obtained with high productivity.
　一方、抽出液を撹拌する時間は、特に限定されず、環式化合物の析出速度に基づいて適宜判断される。一例として、３時間以上７２時間以下程度であるのが好ましく、１０時間以上４８時間以下程度であるのがより好ましい。 On the other hand, the time for stirring the extract is not particularly limited, and is appropriately determined based on the precipitation rate of the cyclic compound. As an example, it is preferably about 3 hours or more and 72 hours or less, and more preferably about 10 hours or more and 48 hours or less.
　なお、晶析処理は、抽出液に、析出させようとする環式化合物またはその誘導体の種晶を添加する操作を含むのが好ましい。このような操作を含むことにより、環式化合物の晶析を促すことができる。その結果、より純度の高い環式化合物を析出させることができる The crystallization treatment preferably includes an operation of adding a seed crystal of a cyclic compound or a derivative thereof to be precipitated to the extract. By including such an operation, crystallization of the cyclic compound can be promoted. As a result, a higher purity cyclic compound can be precipitated.
　また、晶析処理では、抽出液中の溶媒に対する環式化合物の濃度が準安定領域に位置するように、抽出液の温度を操作するのが好ましい。これにより、析出速度を抑えつつ析出させることができるので、不純物の巻き込みが抑えられ、純度の高い結晶が析出する。なお、準安定領域とは、温度および濃度を各軸にとった直交座標系において、溶解度の温度分布を示す溶解度曲線と、過溶解度の温度分布を示す過溶解度曲線と、の間の領域のことをいう。 Further, in the crystallization treatment, it is preferable to control the temperature of the extract so that the concentration of the cyclic compound with respect to the solvent in the extract is located in the metastable region. As a result, it is possible to precipitate while suppressing the precipitation rate, so that the inclusion of impurities is suppressed and crystals with high purity are precipitated. The metastable region is a region between a solubility curve showing the temperature distribution of solubility and a persolubility curve showing the temperature distribution of persolubility in a Cartesian coordinate system with temperature and concentration as each axis. To say.
　そして、準安定領域よりも濃度が高い領域は、不安定領域という。濃度が不安定領域を通過するような経路で温度を変化させた場合には、結晶の純度が低下するおそれがある。このため、最終的に得られる環式化合物の純度が低下するおそれがある。 And the region where the concentration is higher than the metastable region is called the unstable region. If the temperature is changed by a route in which the concentration passes through the unstable region, the purity of the crystal may decrease. Therefore, the purity of the finally obtained cyclic compound may decrease.
　１．８．固液分離工程Ｓ０８
　次に、環式化合物が析出した抽出液に対し、固液分離処理を施す。 1.8. Solid-liquid separation step S08
Next, the extract in which the cyclic compound is precipitated is subjected to a solid-liquid separation treatment.
　固液分離処理としては、例えば、ろ過分離、沈降分離、減圧脱水、加圧脱水等が挙げられるが、特に操作の容易さや分離の正確性の観点からろ過分離が好ましく用いられる。具体的には、遠心ろ過機を用いることができる。
　また、固液分離処理は、バッチ処理であっても連続処理であってもよい。 Examples of the solid-liquid separation treatment include filtration separation, sedimentation separation, vacuum dehydration, pressure dehydration and the like, and filtration separation is particularly preferably used from the viewpoint of ease of operation and separation accuracy. Specifically, a centrifugal filter can be used.
Further, the solid-liquid separation treatment may be a batch treatment or a continuous treatment.
　その後、必要に応じて、貧溶媒を用いて洗浄操作を行った後、乾燥させる。乾燥は、強制乾燥であっても、自然乾燥であってもよい。以上のようにして、抽出液中の環式化合物を分離し、回収する。 Then, if necessary, perform a washing operation using a poor solvent and then dry. The drying may be forced drying or natural drying. As described above, the cyclic compound in the extract is separated and recovered.
　１．９．その他の工程
　また、回収した環式化合物は、追加的に設けられるその他の工程に供されてもよい。 1.9. Other Steps The recovered cyclic compound may be subjected to other steps additionally provided.
　追加的に設けられるその他の工程としては、例えば、前述した再溶解工程、吸着工程と同様の工程を順次行った後、再沈殿工程を行うという一連の工程が挙げられる。 Examples of other steps additionally provided include a series of steps of sequentially performing the same steps as the above-mentioned redissolving step and adsorption step, and then performing a reprecipitation step.
　このうち、再沈殿工程は、再溶解工程と同様の工程および吸着工程と同様の工程を順次行った後、得られた溶液に貧溶媒を添加する工程である。貧溶媒を添加することにより、溶液中では環式化合物の沈殿が得られる。この沈殿を固液分離工程と同様の工程に供することにより、さらに純度を高めた環式化合物を得ることができる。 Of these, the reprecipitation step is a step of sequentially performing the same steps as the redissolution step and the same steps as the adsorption step, and then adding a poor solvent to the obtained solution. By adding the poor solvent, precipitation of the cyclic compound can be obtained in the solution. By subjecting this precipitate to the same step as the solid-liquid separation step, a cyclic compound having further increased purity can be obtained.
　貧溶媒としては、水と混和し、かつ水よりも環式化合物の溶解度が低い溶媒であれば、特に限定されない。
　なお、本実施形態には、上記以外の任意の工程が追加されていてもよい。 The poor solvent is not particularly limited as long as it is miscible with water and has a lower solubility of the cyclic compound than water.
In addition, an arbitrary step other than the above may be added to this embodiment.
　以上のように、本実施形態に係る環式化合物またはその誘導体の製造方法は、環式化合物またはその誘導体を含有する原料液体に乾燥処理を施し、乾燥物を得る乾燥工程である第１乾燥工程と、乾燥物から環式化合物またはその誘導体を抽出用溶媒に抽出し、抽出液を得る抽出工程と、抽出液から環式化合物またはその誘導体を析出させる析出工程と、を有している。そして、乾燥処理は、圧力１０Ｐａ以下において、原料液体を温度６５～１２５℃で加熱する処理である。つまり、かかる乾燥処理は、前述した温度範囲で加熱する真空乾燥法による処理である。 As described above, the method for producing a cyclic compound or a derivative thereof according to the present embodiment is a first drying step, which is a drying step of subjecting a raw material liquid containing the cyclic compound or a derivative thereof to a drying treatment to obtain a dried product. It also has an extraction step of extracting the cyclic compound or its derivative from the dried product into an extraction solvent to obtain an extract, and a precipitation step of precipitating the cyclic compound or its derivative from the extract. The drying treatment is a treatment of heating the raw material liquid at a temperature of 65 to 125 ° C. at a pressure of 10 Pa or less. That is, such a drying treatment is a treatment by a vacuum drying method in which heating is performed in the above-mentioned temperature range.
　このような各工程を有することにより、本実施形態に係る環式化合物またはその誘導体の製造方法は、適度な温度範囲で加熱する真空乾燥法を用いた第１乾燥工程を有しているため、最終的に高純度な環式化合物を高い収率で回収することができる。また、第１乾燥工程、抽出工程および析出工程を経ることで、不純物となる有機成分および無機成分を順次除去することができ、かかる観点でも、高純度化および高収率化を図ることができる。さらに、得られる環式化合物の白色度を高めることもできる。また、真空乾燥法では、特に短時間での乾燥処理が可能であり、かつ、抽出および析出を利用することによって、環式化合物の取り出しに要するエネルギーの削減が可能になる。 By having each of these steps, the method for producing a cyclic compound or a derivative thereof according to the present embodiment has a first drying step using a vacuum drying method of heating in an appropriate temperature range. Finally, a high-purity cyclic compound can be recovered in a high yield. Further, by passing through the first drying step, the extraction step and the precipitation step, the organic component and the inorganic component which are impurities can be sequentially removed, and from this viewpoint as well, high purity and high yield can be achieved. .. Furthermore, the whiteness of the obtained cyclic compound can be increased. Further, in the vacuum drying method, the drying treatment can be performed in a particularly short time, and the energy required for extracting the cyclic compound can be reduced by utilizing extraction and precipitation.
　また、本実施形態に係る原料液体調製工程は、前述したように、原料液体を濃縮する濃縮処理を含む。原料液体調製工程が濃縮処理を含むことにより、原料液体の単位量から回収可能な固体の量の割合、すなわち収率を高めることができる。このため、それ以降の各工程に要する時間やエネルギーを削減することができ、環式化合物の製造効率、すなわち単位時間当たりの環式化合物の生産能力を高めることができる。 Further, the raw material liquid preparation step according to the present embodiment includes a concentration treatment for concentrating the raw material liquid, as described above. By including the concentration treatment in the raw material liquid preparation step, the ratio of the amount of solids that can be recovered from the unit amount of the raw material liquid, that is, the yield can be increased. Therefore, the time and energy required for each subsequent step can be reduced, and the production efficiency of the cyclic compound, that is, the production capacity of the cyclic compound per unit time can be increased.
　さらに、本実施形態に係る環式化合物またはその誘導体の製造方法は、前述したように、再溶解工程および吸着工程を有している。このうち、再溶解工程は、乾燥工程である第１乾燥工程と抽出工程との間、すなわち、第１乾燥工程の後であり、かつ、抽出工程の前に設けられる工程であって、乾燥物を再溶解用溶媒に溶解させ、再溶解液を調製する工程である。一方、吸着工程は、再溶解工程と抽出工程との間、すなわち、再溶解工程の後であり、かつ、抽出工程の前に設けられる工程であって、再溶解液に吸着処理を施す工程である。 Further, the method for producing a cyclic compound or a derivative thereof according to the present embodiment includes a redissolving step and an adsorption step as described above. Of these, the remelting step is a step provided between the first drying step and the extraction step, which are the drying steps, that is, after the first drying step and before the extraction step, and is a dried product. Is a step of preparing a re-dissolved solution by dissolving the above in a re-dissolving solvent. On the other hand, the adsorption step is a step provided between the re-dissolution step and the extraction step, that is, after the re-dissolution step and before the extraction step, and is a step of applying the adsorption treatment to the re-dissolved solution. be.
　このような再溶解工程および吸着工程を有することにより、再溶解液中の不純物、例えば高分子の有機成分等が除去される。その結果、最終的に得られる環式化合物の純度を高めるとともに、環式化合物の着色を抑制することができる。 By having such a redissolving step and an adsorption step, impurities in the redissolving liquid, for example, organic components of a polymer, etc. are removed. As a result, the purity of the finally obtained cyclic compound can be increased, and the coloring of the cyclic compound can be suppressed.
　＜第２実施形態＞
２．環式化合物またはその誘導体の製造方法
　次に、本発明の環式化合物またはその誘導体の製造方法の第２実施形態について説明する。 <Second Embodiment>
2. Method for Producing Cyclic Compound or Derivative thereof Next, a second embodiment of the method for producing a cyclic compound or a derivative thereof of the present invention will be described.
　以下、環式化合物またはその誘導体の製造方法の第２実施形態について説明するが、前記第１実施形態と異なる点を中心に説明し、同様の事項についてはその説明を省略する。 Hereinafter, the second embodiment of the method for producing a cyclic compound or a derivative thereof will be described, but the differences from the first embodiment will be mainly described, and the same matters will be omitted.
　本実施形態に係る環式化合物またはその誘導体の製造方法は、前述した第１実施形態と同様に、原料液体調製工程Ｓ０１と、第１乾燥工程Ｓ０２と、再溶解工程Ｓ０３と、吸着工程Ｓ０４と、第２乾燥工程Ｓ０５と、抽出工程Ｓ０６と、析出工程Ｓ０７と、固液分離工程Ｓ０８と、を有する。本実施形態の環式化合物の製造方法によっても、固体で高純度の環式化合物またはその誘導体を高い収率で製造することができる。以下、各工程について順次説明する。なお、原料液体調製工程Ｓ０１は、前述した第１実施形態の原料液体調製工程Ｓ０１と同様の工程であるため、その説明を省略する。 The method for producing the cyclic compound or its derivative according to the present embodiment is the same as that of the first embodiment described above, that is, the raw material liquid preparation step S01, the first drying step S02, the remelting step S03, and the adsorption step S04. , A second drying step S05, an extraction step S06, a precipitation step S07, and a solid-liquid separation step S08. The method for producing a cyclic compound of the present embodiment can also produce a solid, high-purity cyclic compound or a derivative thereof in a high yield. Hereinafter, each step will be described in sequence. Since the raw material liquid preparation step S01 is the same step as the raw material liquid preparation step S01 of the first embodiment described above, the description thereof will be omitted.
　２．２．第１乾燥工程Ｓ０２
　原料液体調製工程Ｓ０１で得られた原料液体を乾燥させ、乾燥物を得る（乾固）。 2.2. First drying step S02
The raw material liquid obtained in the raw material liquid preparation step S01 is dried to obtain a dried product (dry solid).
　原料液体を乾燥させる方法としては、例えば、前述した、煮沸乾燥法、噴霧乾燥法、伝熱乾燥法、赤外線乾燥法、温風乾燥法、真空乾燥法等が挙げられる。また、これらの乾燥法を含む複数種の乾燥法を組み合わせて適用するようにしてもよい。代表的な４つの乾燥法のうち、煮沸乾燥法、噴霧乾燥法および伝熱乾燥法については、前述した第１実施形態で説明した各方法を用いることができる。以下に、本実施形態の乾燥方法としての真空乾燥法について説明する。 Examples of the method for drying the raw material liquid include the above-mentioned boiling drying method, spray drying method, heat transfer drying method, infrared drying method, warm air drying method, vacuum drying method and the like. Further, a plurality of types of drying methods including these drying methods may be applied in combination. Of the four typical drying methods, as for the boiling drying method, the spray drying method and the heat transfer drying method, each method described in the above-described first embodiment can be used. The vacuum drying method as the drying method of the present embodiment will be described below.
　２．２．１．真空乾燥法
　真空乾燥法では、原料液体を密閉容器に入れ、密閉容器内を減圧する。これにより、原料液体と容器内との溶媒分圧差を大きくし、乾燥を促進させる。その結果、原料液体を短時間で確実に乾燥させ、乾燥物を得ることができる。加えて、低分子の不純物成分を効率よく除去することができるので、最終的に得られる環式化合物の純度や白色度を高めることができる。 2.2.1. Vacuum drying method In the vacuum drying method, the raw material liquid is placed in a closed container and the pressure inside the closed container is reduced. As a result, the difference in solvent partial pressure between the raw material liquid and the inside of the container is increased, and drying is promoted. As a result, the raw material liquid can be reliably dried in a short time to obtain a dried product. In addition, since small molecule impurity components can be efficiently removed, the purity and whiteness of the finally obtained cyclic compound can be increased.
　また、真空乾燥法では、減圧下で処理されることから酸化や燃焼等が生じにくい。このため、環式化合物の酸化等の変性や焦げ付きによる着色等が抑制される。その結果、最終的に得られる環式化合物の純度や白色度を高めることができる。 Also, in the vacuum drying method, oxidation and combustion are unlikely to occur because the treatment is performed under reduced pressure. Therefore, denaturation such as oxidation of the cyclic compound and coloring due to scorching are suppressed. As a result, the purity and whiteness of the finally obtained cyclic compound can be increased.
　なお、真空乾燥法では、必要に応じて、原料液体を加熱するようにしてもよい。その場合の加熱温度は、溶媒の沸点に応じて適宜設定されるが、一例として３０～２００℃程度であるのが好ましく、４０～１５０℃程度であるのがより好ましく、６０～１２０℃程度であるのがさらに好ましい。 In the vacuum drying method, the raw material liquid may be heated if necessary. The heating temperature in that case is appropriately set according to the boiling point of the solvent, but as an example, it is preferably about 30 to 200 ° C., more preferably about 40 to 150 ° C., and about 60 to 120 ° C. It is even more preferable to have it.
　加熱時間は、溶媒の蒸発の進行度合いに応じて適宜設定されるが、一例として１０分～２４時間程度であるのが好ましく、３０分～６時間程度であるのがより好ましい。 The heating time is appropriately set according to the progress of evaporation of the solvent, but as an example, it is preferably about 10 minutes to 24 hours, and more preferably about 30 minutes to 6 hours.
　真空乾燥における密閉容器内の圧力は、大気圧未満であれば特に限定されないが、一例として１００Ｐａ以下であるのが好ましく、２０Ｐａ以下であるのがより好ましく、１０Ｐａ以下であるのがさらに好ましい。これにより、特に効率よく乾燥させることができるので、加熱に伴う環式化合物の変性等を最小限に留めることができる。また、酸化による変性や着色についても最小限に抑えることができる。 The pressure in the closed container in vacuum drying is not particularly limited as long as it is less than atmospheric pressure, but as an example, it is preferably 100 Pa or less, more preferably 20 Pa or less, and further preferably 10 Pa or less. As a result, it can be dried particularly efficiently, so that denaturation of the cyclic compound due to heating can be minimized. In addition, denaturation and coloring due to oxidation can be minimized.
　なお、得られた乾燥物は、必要に応じて、解砕または粉砕されるようにしてもよい。これにより、乾燥物の比表面積が大きくなるため、後述する再溶解工程において環式化合物の溶解効率を高めることができる。 The obtained dried product may be crushed or crushed as needed. As a result, the specific surface area of the dried product is increased, so that the dissolution efficiency of the cyclic compound can be increased in the redissolution step described later.
　なお、本工程では全ての溶媒を除去する必要はなく、一部の溶媒を残存させるようにしてもよい。つまり、第１乾燥工程は、不完全な乾燥物を得る工程であってもよい。 It should be noted that it is not necessary to remove all the solvents in this step, and some solvents may remain. That is, the first drying step may be a step of obtaining an incompletely dried product.
　乾燥物における溶媒の含有率は、３０質量％以下であるのが好ましく、１質量％以上２０質量％以下であるのがより好ましい。これにより、最終的な乾燥に要する時間やエネルギーが抑えられるため、効率のよい処理が可能になる。 The content of the solvent in the dried product is preferably 30% by mass or less, and more preferably 1% by mass or more and 20% by mass or less. As a result, the time and energy required for final drying can be reduced, so that efficient processing becomes possible.
　そして、以上のような乾燥物を得る過程では、溶媒の揮発に伴って主に低分子の有機成分を除去することができる。これにより、最終的に得られる環式化合物の純度を高めることができる。 Then, in the process of obtaining the dried product as described above, mainly small molecule organic components can be removed as the solvent volatilizes. Thereby, the purity of the finally obtained cyclic compound can be increased.
　２．３．再溶解工程Ｓ０３
　次に、得られた乾燥物を再溶解用溶媒に溶解し、溶液（第１溶液）を調製する。溶液を調製することにより、後述する吸着工程が可能になる。 2.3. Redissolution step S03
Next, the obtained dried product is dissolved in a redissolving solvent to prepare a solution (first solution). By preparing the solution, the adsorption step described later becomes possible.
　再溶解用溶媒には、乾燥物を溶解させる良溶媒が用いられる。良溶媒としては、例えば、水、メタノール、ヘキサン、クロロホルム等が挙げられる。 As the redissolving solvent, a good solvent that dissolves the dried product is used. Examples of the good solvent include water, methanol, hexane, chloroform and the like.
　２．４．吸着工程Ｓ０４
　次に、溶液（第１溶液）に対して吸着処理を施すが、それに先立って、溶液に含まれる環式化合物をイオン化させる処理を施す。この処理は、環式化合物のイオン化傾向を利用して、溶液の条件を変更することにより、イオン化率を高める処理である。このような処理を施すことにより、溶液中の環式化合物の存在比を低下させることができる。本実施形態では、吸着処理に供する溶液（第１溶液）の調製に際し、溶液における環式化合物の存在量が、環式化合物のイオンの存在量よりも少なくなるように、溶液を調製する。その結果、その後の吸着処理において、環式化合物が吸着媒体に吸着されてしまい、最終的な環式化合物の収率が低下するのを抑制することができる。 2.4. Adsorption step S04
Next, the solution (first solution) is subjected to an adsorption treatment, but prior to that, a treatment for ionizing the cyclic compound contained in the solution is performed. This treatment is a treatment for increasing the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be reduced. In the present embodiment, when preparing the solution (first solution) to be subjected to the adsorption treatment, the solution is prepared so that the abundance of the cyclic compound in the solution is smaller than the abundance of ions of the cyclic compound. As a result, in the subsequent adsorption treatment, it is possible to prevent the cyclic compound from being adsorbed on the adsorption medium and reduce the yield of the final cyclic compound.
　ここで、溶液において、環式化合物の価数は０である。一方、その環式化合物のイオンは、イオンの種類（化学種）に応じて異なるものの、例えば１価イオン、２価イオンおよび３価イオンを含むとする。これらの価数は、ｐＨ依存性または温度依存性を持つことが知られている。例えば、ｐＨ依存性を持つ場合には、抽出液のｐＨを変更することによって、価数が０になるのか、または、価数が１、２もしくは３になるのか、を制御することが可能になる。これにより、溶液において、環式化合物の存在量と、環式化合物のイオンの存在量と、を適宜制御することができる。 Here, in the solution, the valence of the cyclic compound is 0. On the other hand, the ions of the cyclic compound are different depending on the type (chemical species) of the ions, but include, for example, monovalent ions, divalent ions and trivalent ions. These valences are known to be pH dependent or temperature dependent. For example, when it has a pH dependence, it is possible to control whether the valence becomes 0 or 1, 2 or 3 by changing the pH of the extract. Become. Thereby, the abundance of the cyclic compound and the abundance of ions of the cyclic compound can be appropriately controlled in the solution.
　図２は、溶液中の環式化合物の存在比および溶液中の環式化合物のイオンの存在比とｐＨとの関係の一例を示すグラフである。図２に示すように、ｐＨが高くなるにつれて、価数０の環式化合物の存在比が徐々に低下する一方、価数１のイオンの存在比が徐々に増加している。また、さらにｐＨが高くなると、今度は、価数１のイオンの存在比が徐々に低下する一方、価数２のイオンの存在比が徐々に増加している。その後、さらにｐＨが高くなると、価数２のイオンの存在比が徐々に低下する一方、価数３のイオンの存在比が徐々に増加している。 FIG. 2 is a graph showing an example of the relationship between the abundance ratio of a cyclic compound in a solution, the abundance ratio of ions of a cyclic compound in a solution, and pH. As shown in FIG. 2, as the pH increases, the abundance ratio of the cyclic compound having a valence of 0 gradually decreases, while the abundance ratio of the ion having a valence of 1 gradually increases. Further, when the pH is further increased, the abundance ratio of the ion having a valence of 1 gradually decreases, while the abundance ratio of the ion having a valence of 2 gradually increases. After that, when the pH is further increased, the abundance ratio of ions having a valence of 2 gradually decreases, while the abundance ratio of ions having a valence of 3 gradually increases.
　これらを踏まえると、前述したようにして溶液に含まれる環式化合物をイオン化させる処理を施す際、一例として、溶液のｐＨを操作すればよいことになる。これにより、溶液における環式化合物のイオン化率を制御することができる。 Based on these, when performing the treatment for ionizing the cyclic compound contained in the solution as described above, the pH of the solution may be manipulated as an example. Thereby, the ionization rate of the cyclic compound in the solution can be controlled.
　溶液のｐＨを変更する場合、例えば溶液に酸またはアルカリを添加する。アルカリを添加すると、ｐＨを上昇させることができる。これにより、溶液（第１溶液）における環式化合物のイオン化率を高めることができる。一方、酸を添加すると、ｐＨを低下させることができる。これにより、溶液における環式化合物のイオン化率が低下し、反対に、環式化合物の存在比が高くなる。 When changing the pH of a solution, for example, add an acid or alkali to the solution. The pH can be increased by adding alkali. Thereby, the ionization rate of the cyclic compound in the solution (first solution) can be increased. On the other hand, the addition of acid can lower the pH. As a result, the ionization rate of the cyclic compound in the solution decreases, and conversely, the abundance ratio of the cyclic compound increases.
　アルカリを添加する場合、アルカリ添加後の溶液のｐＨは、５．０～７．５程度であるのが好ましく、５．５～６．５程度であるのがより好ましい。これにより、溶液における環式化合物の存在比を低下させることができる。その結果、後述する吸着処理において、環式化合物が吸着媒体に吸着される確率を低下させることができる。
　アルカリとしては、例えば、水酸化ナトリウム、水酸化カリウム等が挙げられる。 When the alkali is added, the pH of the solution after the addition of the alkali is preferably about 5.0 to 7.5, and more preferably about 5.5 to 6.5. This makes it possible to reduce the abundance ratio of the cyclic compound in the solution. As a result, the probability that the cyclic compound is adsorbed on the adsorption medium can be reduced in the adsorption treatment described later.
Examples of the alkali include sodium hydroxide, potassium hydroxide and the like.
　また、酸としては、例えば、ギ酸、酢酸、塩酸、プロピオン酸、酪酸、吉草酸等が挙げられる。 Examples of the acid include formic acid, acetic acid, hydrochloric acid, propionic acid, butyric acid, valeric acid and the like.
　なお、前述した「溶液（第１溶液）における環式化合物の存在量が、環式化合物のイオンの存在量よりも少ない」とは、前者の存在量を１としたとき、後者の存在量が、前者に対するモル比で１未満であることをいう。この場合、好ましくは、後者の存在量が、前者に対するモル比で０．９以下とされ、より好ましくは０．８以下とされる。これにより、環式化合物が吸着媒体に吸着されてしまう確率をさらに低下させることができる。 The above-mentioned "the abundance of the cyclic compound in the solution (first solution) is smaller than the abundance of ions of the cyclic compound" means that when the abundance of the former is 1, the abundance of the latter is , It means that the molar ratio to the former is less than 1. In this case, the abundance of the latter is preferably 0.9 or less, more preferably 0.8 or less, in terms of the molar ratio with respect to the former. This makes it possible to further reduce the probability that the cyclic compound will be adsorbed on the adsorption medium.
　次に、溶液（第１溶液）に対して吸着処理を施す。吸着処理は、溶液に吸着媒体を接触させ、溶液中の高分子成分等を吸着媒体に吸着させる処理である。これにより、溶液中の不純物、例えば高分子の有機成分等が除去される。その結果、最終的に得られる環式化合物の純度を高めるとともに、着色を抑制することができる。なお、吸着処理において吸着、除去するのは、高分子の有機成分に限定されず、いかなる不純物であってもよい。 Next, the solution (first solution) is subjected to adsorption treatment. The adsorption treatment is a treatment in which the adsorption medium is brought into contact with the solution and the polymer components and the like in the solution are adsorbed on the adsorption medium. As a result, impurities in the solution, for example, organic components of the polymer are removed. As a result, the purity of the finally obtained cyclic compound can be increased and coloring can be suppressed. It should be noted that what is adsorbed and removed in the adsorption treatment is not limited to the organic component of the polymer, and any impurity may be used.
　吸着媒体は、吸着能を有する媒体であれば、特に限定されないが、例えば活性炭、シリカゲル、ゼオライト等である。そして、吸着処理では、溶液に吸着媒体を接触させることができれば、いかなる方法も用いられる。 The adsorption medium is not particularly limited as long as it has an adsorptive ability, but is, for example, activated carbon, silica gel, zeolite, or the like. Then, in the adsorption treatment, any method is used as long as the adsorption medium can be brought into contact with the solution.
　吸着処理における溶液の温度は、例えば３０～１５０℃程度とされる。また、吸着処理の時間は、特に限定されないが、１０分～１０時間程度であるのが好ましい。 The temperature of the solution in the adsorption treatment is, for example, about 30 to 150 ° C. The time of the adsorption treatment is not particularly limited, but is preferably about 10 minutes to 10 hours.
　また、吸着媒体として活性炭を用いる場合、溶液１００ｇに対する活性炭の添加量は、特に限定されないが、０．０１～３．０ｇであるのが好ましく、０．１～１．０ｇであるのがより好ましい。これにより、不純物を高い確率で吸着し、最終的な環式化合物の純度を高めるとともに、着色を抑制することができる。 When activated carbon is used as the adsorption medium, the amount of activated carbon added to 100 g of the solution is not particularly limited, but is preferably 0.01 to 3.0 g, more preferably 0.1 to 1.0 g. .. As a result, impurities can be adsorbed with a high probability, the purity of the final cyclic compound can be increased, and coloring can be suppressed.
　なお、吸着工程の順序は、本実施形態に限定されず、例えば第１乾燥工程の前であってもよく、抽出工程と析出工程との間であってもよい。
　また、吸着処理後の吸着媒体は、ろ過等の固液分離処理によって除去される。 The order of the adsorption steps is not limited to this embodiment, and may be, for example, before the first drying step or between the extraction step and the precipitation step.
Further, the adsorption medium after the adsorption treatment is removed by a solid-liquid separation treatment such as filtration.
　２．５．第２乾燥工程Ｓ０５
　次に、吸着工程を経た溶液（第２溶液）を乾燥させ、乾燥物を得るが、それに先立って、溶液に含まれる環式化合物のイオンを非イオン化させる処理を施す。この処理は、環式化合物のイオン化傾向を利用して、溶液の条件を変更することにより、イオン化率を下げる処理である。このような処理を施すことにより、溶液中の環式化合物の存在比を高めることができる。本実施形態では、吸着工程を経た溶液（第２溶液）の調製に際し、吸着工程を経た溶液（第２溶液）における環式化合物の存在量が、環式化合物のイオンの存在量以上であるように、溶液を調製する。その結果、本工程の後の抽出工程において、環式化合物の収率を高めることができる。 2.5. Second drying step S05
Next, the solution (second solution) that has undergone the adsorption step is dried to obtain a dried product, but prior to that, a treatment for deionizing the ions of the cyclic compound contained in the solution is performed. This treatment is a treatment for lowering the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be increased. In the present embodiment, when preparing the solution (second solution) that has undergone the adsorption step, the abundance of the cyclic compound in the solution (second solution) that has undergone the adsorption step is such that the abundance of the cyclic compound is equal to or greater than the abundance of ions of the cyclic compound. To prepare the solution. As a result, the yield of the cyclic compound can be increased in the extraction step after this step.
　イオン化率を下げる処理としては、例えば、酸を添加する処理が挙げられる。酸添加後の溶液のｐＨは、２．０～４．５程度であるのが好ましく、２．５～３．５程度であるのがより好ましい。これにより、溶液における環式化合物の存在比を高めることができる。その結果、後述する抽出工程において、環式化合物の収率を高めることができる。 Examples of the treatment for lowering the ionization rate include a treatment for adding an acid. The pH of the solution after the addition of the acid is preferably about 2.0 to 4.5, more preferably about 2.5 to 3.5. This makes it possible to increase the abundance ratio of the cyclic compound in the solution. As a result, the yield of the cyclic compound can be increased in the extraction step described later.
　なお、吸着処理に供する溶液（第１溶液）のｐＨと吸着工程を経た溶液（第２溶液）のｐＨとの差は、１．５以上５．０以下であるのが好ましく、２．０以上４．０以下であるのがより好ましい。このようなｐＨの差を設けることにより、吸着工程における環式化合物の吸着確率を低下させ、かつ、抽出工程における環式化合物の収率を高めることができる。その結果、最終的に、環式化合物の収率を特に高めることができる。 The difference between the pH of the solution (first solution) to be subjected to the adsorption treatment and the pH of the solution (second solution) that has undergone the adsorption step is preferably 1.5 or more and 5.0 or less, and 2.0 or more. It is more preferably 4.0 or less. By providing such a difference in pH, it is possible to reduce the adsorption probability of the cyclic compound in the adsorption step and increase the yield of the cyclic compound in the extraction step. As a result, the yield of the cyclic compound can be particularly increased in the end.
　また、前述した「溶液（第２溶液）における環式化合物の存在量が、環式化合物のイオンの存在量以上である」とは、前者の存在量を１としたとき、後者の存在量が、前者に対するモル比で１以上であることをいう。この場合、好ましくは、後者の存在量が、前者に対するモル比で１．１以上とされ、より好ましくは１．２以上とされる。これにより、環式化合物の収率をより高めることができる。 Further, the above-mentioned "the abundance of the cyclic compound in the solution (second solution) is equal to or greater than the abundance of ions of the cyclic compound" means that when the abundance of the former is 1, the abundance of the latter is , It means that the molar ratio to the former is 1 or more. In this case, the abundance of the latter is preferably 1.1 or more, more preferably 1.2 or more, in terms of the molar ratio to the former. Thereby, the yield of the cyclic compound can be further increased.
　また、乾燥物を得るのに先立ち、イオン化率を下げる処理とは別に、またはそれとともに、濃縮処理を施すようにしてもよい。これにより、乾燥に要する時間を短縮するとともに、必要なエネルギーを削減することができる。この濃縮処理は、前述した条件で行うことができる。 Further, prior to obtaining the dried product, a concentration treatment may be performed separately from or in combination with the treatment for lowering the ionization rate. As a result, the time required for drying can be shortened and the required energy can be reduced. This concentration treatment can be performed under the conditions described above.
　以上のような処理を経た後、吸着工程を経た溶液（第２溶液）を乾燥させる。第２乾燥工程は、前述した第１乾燥工程と同様に行えばよいが、その方法は、第１乾燥工程と同じであっても、異なっていてもよい。 After undergoing the above treatment, the solution (second solution) that has undergone the adsorption step is dried. The second drying step may be performed in the same manner as the first drying step described above, but the method may be the same as or different from the first drying step.
　なお、後に説明するが、後述する抽出工程において、固液抽出処理ではなく、液液抽出処理を採用した場合には、本工程を省略することができる。 As will be described later, if a liquid-liquid extraction process is adopted instead of the solid-liquid extraction process in the extraction step described later, this step can be omitted.
　２．６．抽出工程Ｓ０６
　次に、前述した第１実施形態と同様に、固液抽出用の溶媒（抽出用溶媒）により、乾燥物に固液抽出処理を施し、抽出液を得る。 2.6. Extraction step S06
Next, in the same manner as in the first embodiment described above, the dried product is subjected to a solid-liquid extraction treatment with a solvent for solid-liquid extraction (extraction solvent) to obtain an extract.
　２．７．析出工程Ｓ０７
　次に、前述した第１実施形態と同様に、抽出液に析出処理を施し、抽出液の溶質を固体として析出させる。 2.7. Precipitation step S07
Next, the extract is subjected to a precipitation treatment in the same manner as in the first embodiment described above, and the solute of the extract is precipitated as a solid.
　２．８．固液分離工程Ｓ０８
　次に、前述した第１実施形態と同様に、環式化合物が析出した抽出液に対し、固液分離処理を施す。 2.8. Solid-liquid separation step S08
Next, in the same manner as in the first embodiment described above, the extract in which the cyclic compound is precipitated is subjected to a solid-liquid separation treatment.
　２．９．その他の工程
　また、回収した環式化合物は、追加的に設けられるその他の工程に供されてもよい。 2.9. Other Steps The recovered cyclic compound may be subjected to other steps additionally provided.
　追加的に設けられるその他の工程としては、例えば、前述した再溶解工程、吸着工程と同様の工程を順次行った後、再沈殿工程を行うという一連の工程が挙げられる。 Examples of other steps additionally provided include a series of steps of sequentially performing the same steps as the above-mentioned redissolving step and adsorption step, and then performing a reprecipitation step.
　このうち、再沈殿工程は、再溶解工程と同様の工程および吸着工程と同様の工程を順次行った後、得られた溶液に貧溶媒を添加する工程である。貧溶媒を添加することにより、溶液中では環式化合物の沈殿が得られる。この沈殿を固液分離工程と同様の工程に供することにより、さらに純度を高めた環式化合物を得ることができる。 Of these, the reprecipitation step is a step of sequentially performing the same steps as the redissolution step and the same steps as the adsorption step, and then adding a poor solvent to the obtained solution. By adding the poor solvent, precipitation of the cyclic compound can be obtained in the solution. By subjecting this precipitate to the same step as the solid-liquid separation step, a cyclic compound having further increased purity can be obtained.
　貧溶媒としては、水と混和し、かつ水よりも環式化合物の溶解度が低い溶媒であれば、特に限定されない。
　なお、本実施形態には、上記以外の任意の工程が追加されていてもよい。 The poor solvent is not particularly limited as long as it is miscible with water and has a lower solubility of the cyclic compound than water.
In addition, an arbitrary step other than the above may be added to this embodiment.
　以上のように、本実施形態に係る環式化合物またはその誘導体の製造方法は、環式化合物またはその誘導体を含有する原料液体に乾燥処理を施し、乾燥物を得る乾燥工程である第１乾燥工程と、乾燥物を第１溶媒に再溶解し、第１溶液を得る再溶解工程と、第１溶液に対し、吸着体への吸着処理を施すことにより、第２溶液を得る吸着工程と、第２溶液から環式化合物またはその誘導体を析出させる析出工程と、を有する。そして、第１溶液における環式化合物またはその誘導体の存在量が、環式化合物またはその誘導体のイオンの存在量よりも少なくなるように、第１溶液を調製する。 As described above, the method for producing a cyclic compound or a derivative thereof according to the present embodiment is a first drying step, which is a drying step of subjecting a raw material solution containing the cyclic compound or a derivative thereof to a drying treatment to obtain a dried product. A re-dissolution step of redissolving the dried compound in the first solvent to obtain a first solution, and an adsorption step of obtaining a second solution by subjecting the first solution to an adsorbent treatment. It has a precipitation step of precipitating a cyclic compound or a derivative thereof from two solutions. Then, the first solution is prepared so that the abundance of the cyclic compound or its derivative in the first solution is smaller than the abundance of ions of the cyclic compound or its derivative.
　吸着処理に供する第１溶液の調製に際し、環式化合物またはその誘導体の存在量およびそれらのイオンの存在量を前述したように設定することにより、吸着処理において、環式化合物またはその誘導体が吸着媒体に吸着されてしまうのを抑制することができる。これにより、最終的な環式化合物の収率が低下するのを抑制することができる。また、これらの工程を経ることで、環式化合物の精製に要するエネルギーが少なくて済むため、純度の高い環式化合物の取り出しに要するエネルギーの削減が可能になる。 By setting the abundance of the cyclic compound or its derivative and the abundance of its ions as described above in the preparation of the first solution to be subjected to the adsorption treatment, the cyclic compound or its derivative is used as an adsorption medium in the adsorption treatment. It is possible to suppress the adsorption to the compound. As a result, it is possible to suppress a decrease in the yield of the final cyclic compound. Further, by going through these steps, the energy required for purifying the cyclic compound can be reduced, so that the energy required for extracting the highly pure cyclic compound can be reduced.
　また、本実施形態に係る環式化合物またはその誘導体の製造方法では、前述したように、吸着工程を経た後の第２溶液における環式化合物またはその誘導体の存在量が、環式化合物またはその誘導体のイオンの存在量以上になるように、第２溶液を調製する。 Further, in the method for producing a cyclic compound or a derivative thereof according to the present embodiment, as described above, the abundance of the cyclic compound or its derivative in the second solution after the adsorption step is the cyclic compound or its derivative. The second solution is prepared so that the amount of the ions is equal to or greater than the abundance of the ions.
　吸着工程を経た後の第２溶液の調製に際し、環式化合物またはその誘導体の存在量およびそれらのイオンの存在量を前述したように設定することにより、その後の第２乾燥工程を経て固液抽出する際、環式化合物またはその誘導体の取り出し効率を高めることができる。その結果、最終的に環式化合物の収率をより高めることができる。 In the preparation of the second solution after the adsorption step, by setting the abundance of the cyclic compound or its derivative and the abundance of their ions as described above, solid-liquid extraction is performed through the subsequent second drying step. When doing so, the efficiency of extracting the cyclic compound or its derivative can be increased. As a result, the yield of the cyclic compound can be further increased in the end.
　さらに、本実施形態では、吸着処理に供する第１溶液のｐＨが吸着工程を経た第２溶液のｐＨより大きくなるように、第１溶液および第２溶液をそれぞれ調製する。ｐＨは、前述したように、各溶液中の環式化合物の存在比および各溶液中の環式化合物のイオンの存在比を左右する。しかも、図２に示すように、環式化合物の存在比のｐＨ依存性と、イオンの存在比のｐＨ依存性とは、互いに逆の関係を満たしている。したがって、ｐＨを操作することにより、環式化合物の存在量とイオンの存在量との間で、前述したような大小関係を容易に満足させることができる。その結果、環式化合物の収率を容易に高めることができる。 Further, in the present embodiment, the first solution and the second solution are prepared, respectively, so that the pH of the first solution to be subjected to the adsorption treatment is higher than the pH of the second solution that has undergone the adsorption step. As described above, pH affects the abundance ratio of the cyclic compound in each solution and the ion abundance ratio of the cyclic compound in each solution. Moreover, as shown in FIG. 2, the pH dependence of the abundance ratio of the cyclic compound and the pH dependence of the abundance ratio of the ions satisfy the opposite relationship with each other. Therefore, by manipulating the pH, the magnitude relationship as described above can be easily satisfied between the abundance of the cyclic compound and the abundance of ions. As a result, the yield of the cyclic compound can be easily increased.
　＜第３実施形態＞
３．環式化合物またはその誘導体の製造方法
　次に、本発明の環式化合物またはその誘導体の製造方法の第３実施形態について説明する。
　図３は、本発明の第３実施形態に係る環式化合物またはその誘導体の製造方法を説明するための工程図である。 <Third Embodiment>
3. 3. Method for Producing Cyclic Compound or Derivative thereof Next, a third embodiment of the method for producing the cyclic compound or its derivative of the present invention will be described.
FIG. 3 is a process diagram for explaining a method for producing a cyclic compound or a derivative thereof according to a third embodiment of the present invention.
　以下、環式化合物またはその誘導体の製造方法の第３実施形態について説明するが、前記第１実施形態および前記第２実施形態と異なる点を中心に説明し、同様の事項についてはその説明を省略する。 Hereinafter, a third embodiment of a method for producing a cyclic compound or a derivative thereof will be described, but the differences from the first embodiment and the second embodiment will be mainly described, and the description thereof will be omitted for the same matters. do.
　本実施形態に係る環式化合物またはその誘導体の製造方法は、原料液体調製工程Ｓ０１と、第１乾燥工程Ｓ０２と、再溶解工程Ｓ０３と、吸着工程Ｓ０４と、第２乾燥工程Ｓ０５と、抽出工程Ｓ０６と、晶析工程Ｓ０７と、固液分離工程Ｓ０８と、を有する。本実施形態の環式化合物の製造方法によっても、固体で高純度の環式化合物またはその誘導体を高い収率で製造することができる。以下、各工程について順次説明する。なお、原料液体調製工程Ｓ０１は、前述した第１実施形態の原料液体調製工程Ｓ０１と同様の工程であるため、その説明を省略する。 The method for producing the cyclic compound or its derivative according to the present embodiment includes a raw material liquid preparation step S01, a first drying step S02, a redissolving step S03, an adsorption step S04, a second drying step S05, and an extraction step. It has S06, a crystallization step S07, and a solid-liquid separation step S08. The method for producing a cyclic compound of the present embodiment can also produce a solid, high-purity cyclic compound or a derivative thereof in a high yield. Hereinafter, each step will be described in sequence. Since the raw material liquid preparation step S01 is the same step as the raw material liquid preparation step S01 of the first embodiment described above, the description thereof will be omitted.
　３．２．第１乾燥工程Ｓ０２
　原料液体調製工程Ｓ０１で得られた原料液体を乾燥させ、乾燥物を得る（乾固）。 3.2. First drying step S02
The raw material liquid obtained in the raw material liquid preparation step S01 is dried to obtain a dried product (dry solid).
　原料液体を乾燥させる方法としては、例えば、前述した、煮沸乾燥法、噴霧乾燥法、伝熱乾燥法、赤外線乾燥法、温風乾燥法、真空乾燥法等が挙げられる。また、これらの乾燥法を含む複数種の乾燥法を組み合わせて適用するようにしてもよい。代表的な４つの乾燥法である、煮沸乾燥法、噴霧乾燥法、伝熱乾燥法および真空乾燥法については、前述した第２実施形態で説明した各方法を用いることができる。 Examples of the method for drying the raw material liquid include the above-mentioned boiling drying method, spray drying method, heat transfer drying method, infrared drying method, warm air drying method, vacuum drying method and the like. Further, a plurality of types of drying methods including these drying methods may be applied in combination. As for the four typical drying methods, the boiling drying method, the spray drying method, the heat transfer drying method, and the vacuum drying method, each method described in the second embodiment described above can be used.
　３．３．再溶解工程Ｓ０３
　次に、得られた乾燥物を溶媒に溶解し、溶液を調製する。溶液を調製することにより、後述する吸着工程が可能になる。 3.3. Redissolution step S03
Next, the obtained dried product is dissolved in a solvent to prepare a solution. By preparing the solution, the adsorption step described later becomes possible.
　溶媒には、乾燥物を溶解させる良溶媒が用いられる。良溶媒としては、例えば、水、メタノール、ヘキサン、クロロホルム等が挙げられる。 As the solvent, a good solvent that dissolves the dried product is used. Examples of the good solvent include water, methanol, hexane, chloroform and the like.
　３．４．吸着工程Ｓ０４
　次に、溶液に対して吸着処理を施すが、それに先立って、溶液に含まれる環式化合物をイオン化させる処理を施すようにしてもよい。この処理は、環式化合物のイオン化傾向を利用して、溶液の条件を変更することにより、イオン化率を高める処理である。このような処理を施すことにより、溶液中の環式化合物の存在比率を低下させることができる。その結果、その後の吸着処理において、環式化合物が吸着媒体に吸着されてしまい、最終的な環式化合物の収率が低下するのを抑制することができる。 3.4. Adsorption step S04
Next, the solution is subjected to an adsorption treatment, but prior to that, a treatment for ionizing the cyclic compound contained in the solution may be performed. This treatment is a treatment for increasing the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be reduced. As a result, in the subsequent adsorption treatment, it is possible to prevent the cyclic compound from being adsorbed on the adsorption medium and reduce the yield of the final cyclic compound.
　変更する溶液の条件としては、例えば、溶液のｐＨ、溶液の温度等が挙げられる。このうち、溶液のｐＨを変更する場合、例えば溶液に酸またはアルカリを添加する。アルカリを添加すると、ｐＨを上昇させることができる。これにより、溶液における環式化合物のイオン化率を高めることができる。一方、酸を添加すると、ｐＨを低下させることができる。これにより、溶液における環式化合物のイオン化率が低下し、反対に、環式化合物の存在比率が高くなる。 The conditions of the solution to be changed include, for example, the pH of the solution, the temperature of the solution, and the like. Of these, when changing the pH of the solution, for example, an acid or an alkali is added to the solution. The pH can be increased by adding alkali. This makes it possible to increase the ionization rate of the cyclic compound in the solution. On the other hand, the addition of acid can lower the pH. As a result, the ionization rate of the cyclic compound in the solution decreases, and conversely, the abundance ratio of the cyclic compound increases.
　アルカリを添加する場合、アルカリ添加後の溶液のｐＨは、５．０～７．５程度であるのが好ましく、５．５～６．５程度であるのがより好ましい。これにより、溶液における環式化合物の存在比率を低下させることができる。その結果、後述する吸着処理において、環式化合物が吸着媒体に吸着される確率を低下させることができる。
　アルカリとしては、例えば、水酸化ナトリウム、水酸化カリウム等が挙げられる。 When the alkali is added, the pH of the solution after the addition of the alkali is preferably about 5.0 to 7.5, and more preferably about 5.5 to 6.5. This makes it possible to reduce the abundance ratio of the cyclic compound in the solution. As a result, the probability that the cyclic compound is adsorbed on the adsorption medium can be reduced in the adsorption treatment described later.
Examples of the alkali include sodium hydroxide, potassium hydroxide and the like.
　また、酸としては、例えば、ギ酸、酢酸、塩酸、プロピオン酸、酪酸、吉草酸等が挙げられる。 Examples of the acid include formic acid, acetic acid, hydrochloric acid, propionic acid, butyric acid, valeric acid and the like.
　次に、溶液に対して吸着処理を施す。吸着処理は、溶液に吸着媒体を接触させ、溶液中の高分子成分等を吸着媒体に吸着させる処理である。これにより、溶液中の不純物、例えば高分子の有機成分等が除去される。その結果、最終的に得られる環式化合物の純度を高めるとともに、着色を抑制することができる。なお、吸着処理において吸着、除去するのは、高分子の有機成分に限定されず、いかなる不純物であってもよい。 Next, the solution is adsorbed. The adsorption treatment is a treatment in which the adsorption medium is brought into contact with the solution and the polymer components and the like in the solution are adsorbed on the adsorption medium. As a result, impurities in the solution, for example, organic components of the polymer are removed. As a result, the purity of the finally obtained cyclic compound can be increased and coloring can be suppressed. It should be noted that what is adsorbed and removed in the adsorption treatment is not limited to the organic component of the polymer, and any impurity may be used.
　吸着媒体は、吸着能を有する媒体であれば、特に限定されないが、例えば活性炭、シリカゲル、ゼオライト等である。そして、吸着処理では、溶液に吸着媒体を接触させることができれば、いかなる方法も用いられる。 The adsorption medium is not particularly limited as long as it has an adsorptive ability, but is, for example, activated carbon, silica gel, zeolite, or the like. Then, in the adsorption treatment, any method is used as long as the adsorption medium can be brought into contact with the solution.
　吸着処理における溶液の温度は、例えば３０～１５０℃程度とされる。また、吸着処理の時間は、特に限定されないが、１０分～１０時間程度であるのが好ましい。 The temperature of the solution in the adsorption treatment is, for example, about 30 to 150 ° C. The time of the adsorption treatment is not particularly limited, but is preferably about 10 minutes to 10 hours.
　また、吸着媒体として活性炭を用いる場合、溶液１００ｇに対する活性炭の添加量は、特に限定されないが、０．０１～３．０ｇであるのが好ましく、０．１～１．０ｇであるのがより好ましい。これにより、不純物を高い確率で吸着し、最終的な環式化合物の純度を高めるとともに、着色を抑制することができる。 When activated carbon is used as the adsorption medium, the amount of activated carbon added to 100 g of the solution is not particularly limited, but is preferably 0.01 to 3.0 g, more preferably 0.1 to 1.0 g. .. As a result, impurities can be adsorbed with a high probability, the purity of the final cyclic compound can be increased, and coloring can be suppressed.
　なお、本工程は、必要に応じて行えばよく、省略されてもよい。また、吸着工程の順序は、本実施形態に限定されず、例えば第１乾燥工程の前であってもよく、抽出工程と晶析工程との間であってもよい。
　また、吸着処理後の吸着媒体は、ろ過等の固液分離処理によって除去される。 It should be noted that this step may be performed as needed or may be omitted. Further, the order of the adsorption steps is not limited to this embodiment, and may be, for example, before the first drying step or between the extraction step and the crystallization step.
Further, the adsorption medium after the adsorption treatment is removed by a solid-liquid separation treatment such as filtration.
　３．５．第２乾燥工程Ｓ０５
　次に、吸着工程を経た溶液を乾燥させ、乾燥物を得るが、それに先立って、溶液に含まれる環式化合物のイオンを非イオン化させる処理を施すようにしてもよい。この処理は、環式化合物のイオン化傾向を利用して、溶液の条件を変更することにより、イオン化率を下げる処理である。このような処理を施すことにより、溶液中の環式化合物の存在比率を高めることができる。その結果、その後の抽出工程において、環式化合物の収率を高めることができる。 3.5. Second drying step S05
Next, the solution that has undergone the adsorption step is dried to obtain a dried product, but prior to that, a treatment for deionizing the ions of the cyclic compound contained in the solution may be performed. This treatment is a treatment for lowering the ionization rate by changing the conditions of the solution by utilizing the ionization tendency of the cyclic compound. By performing such a treatment, the abundance ratio of the cyclic compound in the solution can be increased. As a result, the yield of the cyclic compound can be increased in the subsequent extraction step.
　イオン化率を下げる処理としては、例えば、酸を添加する処理が挙げられる。酸添加後の溶液のｐＨは、２．０～４．５程度であるのが好ましく、２．５～３．５程度であるのがより好ましい。これにより、溶液における環式化合物の存在比率を高めることができる。その結果、後述する抽出工程において、環式化合物の収率を高めることができる。 Examples of the treatment for lowering the ionization rate include a treatment for adding an acid. The pH of the solution after the addition of the acid is preferably about 2.0 to 4.5, more preferably about 2.5 to 3.5. This makes it possible to increase the abundance ratio of the cyclic compound in the solution. As a result, the yield of the cyclic compound can be increased in the extraction step described later.
　また、乾燥物を得るのに先立ち、イオン化率を下げる処理とは別に、またはそれとともに、濃縮処理を施すようにしてもよい。これにより、乾燥に要する時間を短縮するとともに、必要なエネルギーを削減することができる。この濃縮処理は、前述した条件で行うことができる。 Further, prior to obtaining the dried product, a concentration treatment may be performed separately from or in combination with the treatment for lowering the ionization rate. As a result, the time required for drying can be shortened and the required energy can be reduced. This concentration treatment can be performed under the conditions described above.
　以上のような処理を経た後、吸着工程を経た溶液を乾燥させる。第２乾燥工程は、前述した第１乾燥工程と同様に行えばよいが、その方法は、第１乾燥工程と同じであっても、異なっていてもよい。 After undergoing the above treatment, the solution that has undergone the adsorption step is dried. The second drying step may be performed in the same manner as the first drying step described above, but the method may be the same as or different from the first drying step.
　なお、後に説明するが、後述する抽出工程において、固液抽出処理ではなく、液液抽出処理を採用した場合には、本工程を省略することができる。 As will be described later, if a liquid-liquid extraction process is adopted instead of the solid-liquid extraction process in the extraction step described later, this step can be omitted.
　３．６．抽出工程Ｓ０６
　次に、前述した第１実施形態と同様に、固液抽出用の溶媒（抽出用溶媒）により、乾燥物に固液抽出処理を施し、抽出液を得る。 3.6. Extraction step S06
Next, in the same manner as in the first embodiment described above, the dried product is subjected to a solid-liquid extraction treatment with a solvent for solid-liquid extraction (extraction solvent) to obtain an extract.
　３．７．晶析工程Ｓ０７
　次に、抽出液に晶析処理を施し、抽出液の溶質を固体として析出させる。このような晶析処理によれば、抽出液の溶質の溶解度を下げることによって環式化合物を析出させるというプロセスを経るため、その後の固液分離工程を経ることによって純度の高い環式化合物を回収することができる。このため、純度の高い環式化合物を高い収率で製造することができる。 3.7. Crystallization step S07
Next, the extract is subjected to a crystallization treatment to precipitate the solute of the extract as a solid. According to such a crystallization treatment, a cyclic compound is precipitated by lowering the solubility of the solute in the extract. Therefore, a highly pure cyclic compound is recovered by undergoing a subsequent solid-liquid separation step. can do. Therefore, a highly pure cyclic compound can be produced in a high yield.
　本実施形態に係る晶析処理は、抽出液中の溶媒に対する環式化合物の濃度が準安定領域に位置するように、抽出液の温度を操作する処理である。 The crystallization treatment according to the present embodiment is a treatment in which the temperature of the extract is controlled so that the concentration of the cyclic compound with respect to the solvent in the extract is located in the metastable region.
　図４は、本発明の第３実施形態に係る晶析処理を説明するための図であって、横軸に抽出液の温度、縦軸に抽出液における環式化合物の溶解度をとったとき、これらの間の関係を示す図である。なお、図４は、一例として、抽出液に含まれる溶質である環式化合物としてシキミ酸を、固液抽出用の溶媒としてメタノールを、それぞれ使用したときの例である。 FIG. 4 is a diagram for explaining the crystallization treatment according to the third embodiment of the present invention, in which the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract. It is a figure which shows the relationship between these. In addition, FIG. 4 is an example when shikimic acid is used as a cyclic compound which is a solute contained in the extract and methanol is used as a solvent for solid-liquid extraction.
　図４に示す破線の曲線は、抽出液における環式化合物の溶解度曲線である。この溶解度曲線は、晶析処理によって析出させる環式化合物の溶解度と温度との関係から求められる曲線である。各温度における溶解度は、環式化合物に固有の値であり、各種文献等に記載された値を採用することができる。また、あらかじめ実験によって溶解度曲線を求めることもできる。 The dashed line curve shown in FIG. 4 is the solubility curve of the cyclic compound in the extract. This solubility curve is a curve obtained from the relationship between the solubility and temperature of the cyclic compound precipitated by the crystallization treatment. The solubility at each temperature is a value peculiar to the cyclic compound, and the values described in various documents and the like can be adopted. It is also possible to obtain the solubility curve by experiment in advance.
　図４に示す実線の曲線は、抽出液における環式化合物の過溶解度曲線である。この過溶解度曲線は、環式化合物の過溶解度と温度との関係から実験によって求められる曲線である。そして、過溶解度とは、その温度において、自然発生的に結晶が析出し始める濃度のことをいう。つまり、一次核化が生じる濃度の最低値のことをいう。したがって、各温度において過溶解度を超えた濃度領域は、一次核化が生じやすい不安定領域である。不安定領域では、結晶が急速に析出しやすいため、不純物を巻き込みやすい。このため、析出した環式化合物では、純度が低下するという懸念がある。 The solid line curve shown in FIG. 4 is the persolubility curve of the cyclic compound in the extract. This persolubility curve is a curve obtained by experiments from the relationship between the persolubility of the cyclic compound and the temperature. The hypersolubility refers to the concentration at which crystals start to precipitate spontaneously at that temperature. In other words, it is the lowest concentration at which primary nucleation occurs. Therefore, the concentration region exceeding the persolubility at each temperature is an unstable region where primary nucleation is likely to occur. In the unstable region, crystals are likely to precipitate rapidly, so that impurities are likely to be involved. Therefore, there is a concern that the purity of the precipitated cyclic compound may decrease.
　一方、前述した準安定領域とは、図４において、溶解度曲線と過溶解度曲線との間にある領域のことをいう。したがって、準安定領域は、過溶解状態でありつつも、一次核化が発生しにくい温度および濃度の領域である。このため、準安定領域内で環式化合物を晶析することにより、不純物の巻き込みが抑えられた結晶を析出させることができる。その結果、最終的に、純度の高い環式化合物を得ることができる。 On the other hand, the metastable region described above refers to a region between the solubility curve and the persolubility curve in FIG. Therefore, the metastable region is a region of temperature and concentration at which primary nucleation is unlikely to occur even though it is in a hyperdissolved state. Therefore, by crystallizing the cyclic compound in the metastable region, it is possible to precipitate crystals in which the inclusion of impurities is suppressed. As a result, a highly pure cyclic compound can be finally obtained.
　本実施形態では、晶析処理において抽出液の温度を操作する際、抽出液における環式化合物の溶解度と温度との関係が準安定領域に位置するように、抽出液の温度を操作する。 In the present embodiment, when the temperature of the extract is manipulated in the crystallization treatment, the temperature of the extract is manipulated so that the relationship between the solubility of the cyclic compound in the extract and the temperature is located in the metastable region.
　図４では、一例として、抽出液を６０℃に加熱した状態Ｃ１から晶析処理を開始する。状態Ｃ１は、準安定領域内に位置している。すなわち、温度６０℃においてメタノールに対するシキミ酸の濃度は、溶解度より高く、過溶解度より低い。 In FIG. 4, as an example, the crystallization treatment is started from the state C1 in which the extract is heated to 60 ° C. State C1 is located in the metastable region. That is, at a temperature of 60 ° C., the concentration of shikimic acid with respect to methanol is higher than the solubility and lower than the hypersolubility.
　次に、状態Ｃ１から抽出液の温度を１０℃上昇させる。この上昇の過程では、溶媒であるメタノールの沸点を超えることになる。このため、抽出液では、メタノールの揮発が進む。これにより、抽出液が濃縮されるため、抽出液の濃度が徐々に上昇する。そして、温度が７０℃に達すると、状態Ｃ２に移行する。この状態Ｃ２も、準安定領域内に位置している。 Next, the temperature of the extract is raised by 10 ° C. from the state C1. In the process of this rise, the boiling point of methanol, which is a solvent, is exceeded. Therefore, in the extract, the volatilization of methanol proceeds. As a result, the extract is concentrated, so that the concentration of the extract gradually increases. Then, when the temperature reaches 70 ° C., the state shifts to the state C2. This state C2 is also located in the metastable region.
　次に、状態Ｃ２から抽出液の温度を１０℃低下させる。このときの冷却速度は、特に限定されないが、０．１℃／分以上５．０℃／分以下程度とする。これにより、不純物の巻き込みを抑えつつ、かつ、効率よくシキミ酸を析出させることができるので、最終的に高純度のシキミ酸が生産性よく得られる。そして、温度が６０℃まで低下すると、状態Ｃ３に移行する。この状態Ｃ３も、準安定領域内に位置している。 Next, the temperature of the extract is lowered by 10 ° C. from the state C2. The cooling rate at this time is not particularly limited, but is about 0.1 ° C./min or more and 5.0 ° C./min or less. As a result, shikimic acid can be efficiently precipitated while suppressing the inclusion of impurities, so that high-purity shikimic acid can be finally obtained with high productivity. Then, when the temperature drops to 60 ° C., the state shifts to the state C3. This state C3 is also located in the metastable region.
　ここで、状態Ｃ３にある抽出液に、シキミ酸の種晶を添加する。種晶は、晶析処理において核となり、シキミ酸の晶析を促すために用いられる。種晶としては、例えば粉末状、顆粒状、塊状の結晶が用いられる。なお、種晶の添加は、必要に応じて行えばよく、省略されてもよい。 Here, the seed crystal of shikimic acid is added to the extract in the state C3. The seed crystal becomes a nucleus in the crystallization treatment and is used to promote the crystallization of shikimic acid. As the seed crystal, for example, powdery, granular, or lumpy crystals are used. The addition of seed crystals may be performed as needed or may be omitted.
　次に、状態Ｃ３から抽出液を所定時間放置する。これにより、種晶を核として、シキミ酸が析出する。そして、抽出液の放置を終えると、状態Ｃ４に移行する。この状態Ｃ４も、準安定領域内に位置している。 Next, the extract is left for a predetermined time from the state C3. As a result, shikimic acid is precipitated with the seed crystal as the nucleus. Then, when the leaving of the extract is finished, the state shifts to the state C4. This state C4 is also located in the metastable region.
　抽出液を放置する時間は、特に限定されず、シキミ酸の析出速度に基づいて適宜判断される。一例として、３時間以上７２時間以下程度であるのが好ましく、１０時間以上４８時間以下程度であるのがより好ましい。 The time for leaving the extract to stand is not particularly limited, and is appropriately determined based on the precipitation rate of shikimic acid. As an example, it is preferably about 3 hours or more and 72 hours or less, and more preferably about 10 hours or more and 48 hours or less.
　また、抽出液を放置している最中には、抽出液を撹拌するのが好ましい。これにより、抽出液の濃度を均一にすることができ、シキミ酸の析出速度が低下しにくくなる。そして、効率よく高純度のシキミ酸を析出させることができる。 In addition, it is preferable to stir the extract while the extract is left unattended. As a result, the concentration of the extract can be made uniform, and the precipitation rate of shikimic acid is less likely to decrease. Then, high-purity shikimic acid can be efficiently precipitated.
　次に、状態Ｃ４から抽出液の温度を２０℃低下させる。このときの冷却速度も、前述した範囲内であるのが好ましい。そして、温度が４０℃まで低下すると、状態Ｃ５に移行する。この状態Ｃ５も、準安定領域内に位置している。 Next, the temperature of the extract is lowered by 20 ° C. from the state C4. The cooling rate at this time is also preferably within the above-mentioned range. Then, when the temperature drops to 40 ° C., the state shifts to the state C5. This state C5 is also located in the metastable region.
　次に、状態Ｃ５から抽出液を所定時間放置する。これにより、抽出液に含まれていたシキミ酸の結晶がさらに成長し、または、新たな結晶が析出する。そして、抽出液の放置を終えると、状態Ｃ６に移行する。この状態Ｃ６も、準安定領域内に位置している。抽出液を放置する時間は、特に限定されず、シキミ酸の析出速度に基づいて適宜判断される。一例として、前述した範囲内であるのが好ましい。 Next, the extract is left for a predetermined time from the state C5. As a result, the crystals of shikimic acid contained in the extract grow further, or new crystals are precipitated. Then, when the leaving of the extract is finished, the state shifts to the state C6. This state C6 is also located in the metastable region. The time for leaving the extract to stand is not particularly limited, and is appropriately determined based on the precipitation rate of shikimic acid. As an example, it is preferably within the above range.
　次に、状態Ｃ６から抽出液の温度を３０℃低下させる。このときの冷却速度も、前述した範囲内であるのが好ましい。そして、温度が１０℃まで低下すると、状態Ｃ７に移行する。この状態Ｃ７も、準安定領域内に位置している。 Next, the temperature of the extract is lowered by 30 ° C. from the state C6. The cooling rate at this time is also preferably within the above-mentioned range. Then, when the temperature drops to 10 ° C., the state shifts to the state C7. This state C7 is also located in the metastable region.
　次に、状態Ｃ７から抽出液を所定時間放置する。これにより、抽出液に含まれていたシキミ酸の結晶がさらに成長し、または、新たな結晶が析出する。そして、抽出液の放置を終えると、状態Ｃ８に移行する。この状態Ｃ８も、準安定領域内に位置している。抽出液を放置する時間は、特に限定されず、シキミ酸の析出速度に基づいて適宜判断される。一例として、前述した範囲内であるのが好ましい。 Next, the extract is left for a predetermined time from the state C7. As a result, the crystals of shikimic acid contained in the extract grow further, or new crystals are precipitated. Then, when the leaving of the extract is finished, the state shifts to the state C8. This state C8 is also located in the metastable region. The time for leaving the extract to stand is not particularly limited, and is appropriately determined based on the precipitation rate of shikimic acid. As an example, it is preferably within the above range.
　以上のような状態Ｃ１から状態Ｃ８に至るまでの経路をたどるように、一連の温度操作を行い、最終的には抽出液に含まれる環式化合物の多くを析出させることができる。 A series of temperature operations can be performed so as to follow the path from the state C1 to the state C8 as described above, and finally most of the cyclic compounds contained in the extract can be precipitated.
　なお、前述した第１乾燥工程、再溶解工程、吸着工程、第２乾燥工程および抽出工程は、必要に応じて行えばよく、例えば原料液体調製工程で用意する原料液体が、すでに環式化合物が精製された状態で含まれている液体である場合には、これらの工程が省略されてもよい。その場合、晶析工程は、かかる原料液体から環式化合物を析出させる工程となる。したがって、上述した原料液体、および原料液体を出発して得られる、溶液、抽出液等の各種液体は、いずれも原料液体とみなすことができる。 The above-mentioned first drying step, redissolving step, adsorption step, second drying step and extraction step may be performed as needed. For example, the raw material liquid prepared in the raw material liquid preparation step is already a cyclic compound. These steps may be omitted if the liquid is contained in a purified state. In that case, the crystallization step is a step of precipitating the cyclic compound from the raw material liquid. Therefore, the above-mentioned raw material liquid and various liquids such as a solution and an extract obtained by starting from the raw material liquid can be regarded as the raw material liquid.
　以上を踏まえると、本実施形態に係る環式化合物またはその誘導体の製造方法は、環式化合物またはその誘導体と溶媒とを含有する原料液体の温度を操作する晶析処理により、原料液体から環式化合物またはその誘導体を析出させる晶析工程を有している。そして、晶析処理は、溶媒に対する環式化合物またはその誘導体の濃度が準安定領域に位置するように、原料液体の温度を操作する処理である。 Based on the above, the method for producing a cyclic compound or a derivative thereof according to the present embodiment is a cyclic compound from the raw material liquid by a crystallization treatment for controlling the temperature of the raw material liquid containing the cyclic compound or its derivative and a solvent. It has a crystallization step of precipitating a compound or a derivative thereof. The crystallization treatment is a treatment in which the temperature of the raw material liquid is controlled so that the concentration of the cyclic compound or its derivative with respect to the solvent is located in the metastable region.
　このような晶析工程を有することにより、本実施形態に係る環式化合物またはその誘導体の製造方法は、後述する固液分離工程を経て、最終的に高純度な環式化合物を高い収率で回収することができる。また、効率よく回収することができるため、回収に要するエネルギーを減らすことができ、エネルギー効率の観点からも有用である。 By having such a crystallization step, the method for producing a cyclic compound or a derivative thereof according to the present embodiment finally obtains a high-purity cyclic compound in a high yield through a solid-liquid separation step described later. It can be recovered. In addition, since it can be efficiently recovered, the energy required for recovery can be reduced, which is useful from the viewpoint of energy efficiency.
　なお、晶析処理では、温度の操作の他に、抽出液のｐＨを調整する操作、抽出液が置かれる周辺の圧力を調整する操作、種類が異なる溶媒を添加する操作等のうちの少なくとも１つ以上の操作が追加されてもよい。 In the crystallization treatment, in addition to the temperature operation, at least one of an operation of adjusting the pH of the extract, an operation of adjusting the pressure around the place where the extract is placed, an operation of adding a different type of solvent, and the like. One or more operations may be added.
　晶析処理において操作される温度範囲は、環式化合物の組成や溶媒の種類等に応じて異なり、特に限定されないが、例えば５～８０℃程度であるのが好ましく、１０～７０℃程度であるのがより好ましい。これにより、晶析処理の能力と収率とを両立することができる。 The temperature range operated in the crystallization treatment varies depending on the composition of the cyclic compound, the type of solvent, and the like, and is not particularly limited, but is preferably about 5 to 80 ° C., for example, about 10 to 70 ° C. Is more preferable. This makes it possible to achieve both the capacity and yield of the crystallization treatment.
　なお、晶析処理は、バッチ処理であっても連続処理であってもよい。また、晶析処理には、例えば公知の撹拌槽を用いることができる。 The crystallization treatment may be a batch treatment or a continuous treatment. Further, for the crystallization treatment, for example, a known stirring tank can be used.
　また、本実施形態に係る晶析処理は、原料液体である抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を含む。このような操作を繰り返し行うことにより、比較的簡単な操作で、抽出液から無駄なく環式化合物を析出させることができる。これにより、最終的に高純度な環式化合物を高い収率で回収することができる。 Further, the crystallization treatment according to the present embodiment includes an operation of lowering the temperature of the extract which is the raw material liquid and an operation of stirring the extract. By repeating such an operation, the cyclic compound can be precipitated from the extract without waste with a relatively simple operation. As a result, a high-purity cyclic compound can be finally recovered in a high yield.
　なお、図４の例では、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を３回ずつ行っているが、この回数は特に限定されず、２回以下でも、４回以上であってもよい。ただし、収率をより高めるという観点では、２回以上ずつであるのが好ましく、３回以上ずつであるのがより好ましい。 In the example of FIG. 4, the operation of lowering the temperature of the extract and the operation of stirring the extract are performed three times each, but the number of times is not particularly limited, and even if it is two times or less, it is four times. It may be the above. However, from the viewpoint of further increasing the yield, it is preferably 2 times or more, and more preferably 3 times or more.
　また、温度を低下させる操作における最大低下幅も、特に限定されず、操作の回数に応じて適宜選択される。一例としては、５０℃以下であるのが好ましく、５．０℃以上４０℃以下であるのがより好ましい。これにより、溶解度曲線や過溶解度曲線の傾きに応じた温度操作が可能になり、かつ、急激な晶析を防止することで純度の低下が生じるのを抑制することができる。 Further, the maximum reduction width in the operation of lowering the temperature is not particularly limited, and is appropriately selected according to the number of operations. As an example, the temperature is preferably 50 ° C. or lower, and more preferably 5.0 ° C. or higher and 40 ° C. or lower. This makes it possible to control the temperature according to the slope of the solubility curve or the persolubility curve, and it is possible to suppress a decrease in purity by preventing abrupt crystallization.
　なお、晶析処理において、抽出液の温度および抽出液における環式化合物の濃度を、継続的にモニターし、温度の操作にフィードバックするようにしてもよく、継続的なモニターは行わないものの、過去の実績等に基づいて操作するようにしてもよい。これにより、温度および濃度をリアルタイムに監視しつつ、その監視結果に応じた操作が可能になる。これにより、全体の所要時間をより短縮しつつ、純度の高い環式化合物の析出が可能になる。 In the crystallization treatment, the temperature of the extract and the concentration of the cyclic compound in the extract may be continuously monitored and fed back to the temperature operation. The operation may be performed based on the actual results of. This makes it possible to monitor the temperature and concentration in real time and operate according to the monitoring result. This makes it possible to precipitate a highly pure cyclic compound while further shortening the overall required time.
　また、２つ以上の操作を、時間的に同時に行うようにしてもよい。例えば、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を時間的に同時に行うようにしてもよい。これにより、全体の所要時間をより短縮することができる。 Also, two or more operations may be performed simultaneously in time. For example, the operation of lowering the temperature of the extract and the operation of stirring the extract may be performed simultaneously in time. As a result, the total required time can be further shortened.
　また、本実施形態に係る晶析処理は、前述したように、原料液体である抽出液に、析出させようとする環式化合物またはその誘導体の種晶を添加する操作を含む。このような操作を含むことにより、準安定領域内であっても環式化合物の晶析を促すことができる。その結果、より純度の高い環式化合物を析出させることができる。 Further, the crystallization treatment according to the present embodiment includes an operation of adding a seed crystal of a cyclic compound or a derivative thereof to be precipitated to the extract which is the raw material liquid, as described above. By including such an operation, crystallization of the cyclic compound can be promoted even in the metastable region. As a result, a higher-purity cyclic compound can be precipitated.
　３．８．固液分離工程Ｓ０８
　次に、前述した第１実施形態と同様に、環式化合物が析出した抽出液に対し、固液分離処理を施す。 3.8. Solid-liquid separation step S08
Next, in the same manner as in the first embodiment described above, the extract in which the cyclic compound is precipitated is subjected to a solid-liquid separation treatment.
　３．９．その他の工程
　また、回収した環式化合物は、追加的に設けられるその他の工程に供されてもよい。 3.9. Other Steps The recovered cyclic compound may be subjected to other steps additionally provided.
　追加的に設けられるその他の工程としては、例えば、前述した再溶解工程、吸着工程と同様の工程を順次行った後、再沈殿工程を行うという一連の工程が挙げられる。 Examples of other steps additionally provided include a series of steps of sequentially performing the same steps as the above-mentioned redissolving step and adsorption step, and then performing a reprecipitation step.
　このうち、再沈殿工程は、再溶解工程と同様の工程および吸着工程と同様の工程を順次行った後、得られた溶液に貧溶媒を添加する工程である。貧溶媒を添加することにより、溶液中では環式化合物の沈殿が得られる。この沈殿を固液分離工程と同様の工程に供することにより、さらに純度を高めた環式化合物を得ることができる。 Of these, the reprecipitation step is a step of sequentially performing the same steps as the redissolution step and the same steps as the adsorption step, and then adding a poor solvent to the obtained solution. By adding the poor solvent, precipitation of the cyclic compound can be obtained in the solution. By subjecting this precipitate to the same step as the solid-liquid separation step, a cyclic compound having further increased purity can be obtained.
　貧溶媒としては、水と混和し、かつ水よりも環式化合物の溶解度が低い溶媒であれば、特に限定されない。
　なお、本実施形態には、上記以外の任意の工程が追加されていてもよい。
The poor solvent is not particularly limited as long as it is miscible with water and has a lower solubility of the cyclic compound than water.
In addition, an arbitrary step other than the above may be added to this embodiment.
４．環式化合物またはその誘導体
　次に、前述した実施形態に係る環式化合物の製造方法で製造される環式化合物の一例について説明する。
　かかる環式化合物は、例えば下記式（１）で表される化合物である。 4. Cyclic compound or derivative thereof Next, an example of the cyclic compound produced by the method for producing a cyclic compound according to the above-described embodiment will be described.
Such a cyclic compound is, for example, a compound represented by the following formula (1).
Figure JPOXMLDOC01-appb-C000001
 ［式（１）中、環Ａは、飽和環、部分飽和環もしくは芳香環の５員環、飽和環、部分飽和環もしくは芳香環の６員環、または、５員環もしくは６員環を含む縮合環であり、Ｘは単結合または１つ以上の炭素数を含む結合であり、Ｙは水素原子またはアルキル基、Ｒ２～Ｒ６（環Ａが５員環の場合はＲ２～Ｒ５）は、独立して、水素原子、水酸基、アミノ基、アルコキシ基、カルボキシル基またはカルボニル基である。］
Figure JPOXMLDOC01-appb-C000001
 [In the formula (1), the ring A includes a saturated ring, a partially saturated ring or a 5-membered ring of an aromatic ring, a saturated ring, a 6-membered ring of a partially saturated ring or an aromatic ring, or a 5-membered ring or a 6-membered ring. It is a fused ring, X is a single bond or a bond containing one or more carbon atoms, Y is a hydrogen atom or an alkyl group, R 2 to R 6 (R 2 to R 5 when ring A is a 5-membered ring). ) Are independently hydrogen atoms, hydroxyl groups, amino groups, alkoxy groups, carboxyl groups or carbonyl groups. ]
　飽和環、部分飽和環もしくは芳香環の５員環としては、例えば、フラン構造、チオフェン構造、ピロール構造、ピロリジン構造、テトラヒドロフラン構造、２，３－ジヒドロフラン構造、ピラゾール構造、イミダゾール構造、オキサゾール構造、イソオキサゾール構造、チアゾール構造、イソチアゾール構造等が挙げられる。 Examples of the 5-membered ring of the saturated ring, the partially saturated ring or the aromatic ring include a furan structure, a thiophene structure, a pyrrole structure, a pyrrolidine structure, a tetrahydrofuran structure, a 2,3-dihydrofuran structure, a pyrazole structure, an imidazole structure and an oxazole structure. Examples thereof include an isooxazole structure, a thiazole structure, and an isothiazole structure.
　飽和環の６員環としては、例えば、シクロヘキサン構造のような炭化水素系飽和環、ピペリジン構造、ピペラジン構造、トリアジナン構造、テトラジナン構造、ペンタジナン構造、キヌクリジン構造のような含窒素飽和環、テトラヒドロピラン構造、モルホリン構造のような含酸素飽和環、テトラヒドロチオピラン構造のような含硫黄飽和環等が挙げられる。 Examples of the 6-membered ring of the saturated ring include a hydrocarbon-based saturated ring such as a cyclohexane structure, a piperidine structure, a piperazine structure, a triadinan structure, a tetradinane structure, a pentadinane structure, and a nitrogen-containing saturated ring such as a quinuclidine structure, and a tetrahydropyran structure. , An oxygen-containing saturated ring such as a morpholine structure, a sulfur-containing saturated ring such as a tetrahydropyran structure, and the like.
　部分飽和環の６員環としては、シクロヘキセン構造、シクロヘキサジエン構造のような炭化水素系部分飽和環、ピペリジン構造のような含窒素部分飽和環、ピラン構造のような含酸素部分飽和環、チアジン構造のような含硫黄部分飽和環等が挙げられる。 The 6-membered ring of the partially saturated ring includes a cyclohexene structure, a hydrocarbon-based partially saturated ring such as a cyclohexadiene structure, a nitrogen-containing partially saturated ring such as a piperidine structure, an oxygen-containing partially saturated ring such as a pyran structure, and a thiazine structure. Such as sulfur-containing partially saturated ring and the like can be mentioned.
　芳香環の６員環としては、ベンゼン構造のような炭化水素系芳香環、ピリジン構造、ピリダジン構造、ピリミジン構造、ピラジン構造、トリアジン構造、テトラジン構造、ペンタジン構造のような含窒素芳香環（含窒素不飽和環）等が挙げられる。 The 6-membered ring of the aromatic ring includes a hydrocarbon-based aromatic ring such as a benzene structure, a pyridine structure, a pyridazine structure, a pyrimidine structure, a pyrazine structure, a triazine structure, a tetrazine structure, and a nitrogen-containing aromatic ring (nitrogen-containing structure) such as a pentazine structure. (Unsaturated ring) and the like.
　縮合環としては、例えば６員環と５員環との縮合環、２つの６員環の縮合環等が挙げられる。このうち、６員環と５員環との縮合環としては、例えば、インドール、インドレニン、インドリン、イソインドール、イソインドレニン、イソインドリン、イソドリジン、プリン、インドリジジンのようなインドール系構造が挙げられる。また、２つの６員環の縮合環としては、例えば、キノリン、イソキノリン、キノリジジン、キノキサリン、シンノリン、キナゾリン、フタラジン、ナフチリジン、プテリジンのようなキノリン系構造が挙げられる。 Examples of the fused ring include a fused ring of a 6-membered ring and a 5-membered ring, a fused ring of two 6-membered rings, and the like. Among these, examples of the fused ring of the 6-membered ring and the 5-membered ring include indole-based structures such as indole, indorenin, indole, isoindole, isoindrenin, isoindoline, isodrinine, purine, and indolizidine. .. Examples of the fused ring of the two 6-membered rings include quinoline-based structures such as quinoline, isoquinoline, quinolizidine, quinoxaline, cinnoline, quinazoline, phthalazine, diazanaphthalene, and pteridine.
　Ｘは、単結合または１つ以上の炭素数を含む結合である。
　Ｘが単結合である場合、環Ａの環構成原子に対して酸素原子が直接結合している。 X is a single bond or a bond containing one or more carbon atoms.
When X is a single bond, the oxygen atom is directly bonded to the ring-constituting atom of ring A.
　一方、１つ以上の炭素数を含む結合としては、例えば、炭素数１～４の炭化水素基、エーテル結合、エステル結合、アミド結合、カルボニル基、ビニリデン基等が挙げられ、これらのうちの１種または２種以上を組み合わせたものとされる。 On the other hand, examples of the bond containing one or more carbon atoms include a hydrocarbon group having 1 to 4 carbon atoms, an ether bond, an ester bond, an amide bond, a carbonyl group, a vinylidene group, and the like, and one of them. It is considered to be a species or a combination of two or more species.
　このうち、炭素数１～４の炭化水素基は、直鎖または分枝鎖のいずれであってもよく、飽和または不飽和のいずれであってもよい。なお、炭化水素基の水素原子は、炭素数１～２のアルキル基、水酸基、アミノ基、カルボキシル基、ハロゲン原子等の置換基で置換されていてもよい。 Of these, the hydrocarbon group having 1 to 4 carbon atoms may be either a straight chain or a branched chain, and may be either saturated or unsaturated. The hydrogen atom of the hydrocarbon group may be substituted with a substituent such as an alkyl group having 1 to 2 carbon atoms, a hydroxyl group, an amino group, a carboxyl group, or a halogen atom.
　なお、Ｘには、上述した結合に加え、任意の原子または原子団が含まれていてもよい。例えば、Ｘは、カルボニル基および１つ以上の炭素数を含む結合を含む原子団であってもよい。 Note that X may contain any atom or atomic group in addition to the above-mentioned bond. For example, X may be an atomic group containing a carbonyl group and a bond containing one or more carbon atoms.
　Ｙは、水素原子またはアルキル基である。アルキル基の炭素数は好ましくは１～１２とされ、より好ましくは１～４とされる。 Y is a hydrogen atom or an alkyl group. The number of carbon atoms of the alkyl group is preferably 1 to 12, and more preferably 1 to 4.
　環Ａが６員環である場合、Ｒ２～Ｒ６は、独立して、水素原子、水酸基、アミノ基、アルコキシ基、カルボキシル基またはカルボニル基である。また、環Ａが５員環である場合、Ｒ２～Ｒ５は、独立して、水素原子、水酸基、アミノ基、アルコキシ基、カルボキシル基またはカルボニル基である。 When ring A is a 6-membered ring, R 2 to R 6 are independently hydrogen atoms, hydroxyl groups, amino groups, alkoxy groups, carboxyl groups or carbonyl groups. When the ring A is a 5-membered ring, R 2 to R 5 are independently hydrogen atoms, hydroxyl groups, amino groups, alkoxy groups, carboxyl groups or carbonyl groups.
　なお、環Ａが６員環である場合のＲ２～Ｒ６のいずれか、または、環Ａが５員環である場合のＲ２～Ｒ５のいずれか、がカルボニル基である場合、環Ａの環構成原子が炭素原子であり、かつ、その炭素原子と酸素原子との間が二重結合になっている構造を指して、カルボニル基という。 If any of R 2 to R 6 when the ring A is a 6-membered ring , or any of R 2 to R 5 when the ring A is a 5-membered ring is a carbonyl group, the ring is a ring. A carbonyl group refers to a structure in which the ring-constituting atom of A is a carbon atom and the carbon atom and the oxygen atom have a double bond.
　環式化合物の具体例としては、例えば、安息香酸、フタル酸、イソフタル酸、テレフタル酸、ヘミメリット酸、トリメリット酸、トリメシン酸、メロファン酸、プレーニト酸、ピロメリット酸、フェニル酢酸、ヒドロキシフェニル酢酸、フェニル酪酸（フェニルラクテート）、ヒドロキシフェニル酪酸、フェニルピルビン酸、ヒドロキシフェニルピルビン酸、フェニル乳酸、ヒドロキシフェニル乳酸、アントラニル酸、ヒドロアトロパ酸、アトロパ酸、ヒドロケイ皮酸（クマル酸）、ケイ皮酸、サリチル酸（２－ヒドロキシ安息香酸）、ｍ－サリチル酸（３－ヒドロキシ安息香酸）、ｐ－サリチル酸（４－ヒドロキシ安息香酸）、メトキシ安息香酸、アミノ安息香酸、ヒドロキシ安息香酸、ピロカテク酸（２，３－ジヒドロキシ安息香酸）、β－レソルシル酸（２，４－ジヒドロキシ安息香酸）、ゲンチジン酸（２，５－ジヒドロキシ安息香酸）、γ－レソルシル酸（２，６－ジヒドロキシ安息香酸）、プロトカテク酸（３，４－ジヒドロキシ安息香酸）、α－レソルシル酸（３，５－ジヒドロキシ安息香酸）、トリヒドロキシ安息香酸、バニリン酸（４－ヒドロキシ－３－メトキシ安息香酸）、イソバニリン酸（３－ヒドロキシ－４－メトキシ安息香酸）、ベラトルム酸、没食子酸、シリング酸、アサロン酸、マンデル酸、バニルマンデル酸、アニス酸、ホモプロトカテク酸、ホモバニリン酸、ホモイソバニリン酸、ホモベラトルム酸、ホモフタル酸、ホモイソフタル酸、ホモテレフタル酸、フタロン酸、イソフタロン酸、テレフタロン酸、アトロラクチン酸、トロパ酸、メリロト酸、フロレト酸、ジヒドロカフェー酸、ヒドロフェルラ酸、ヒドロイソフェルラ酸、ウンベル酸、カフェー酸（コーヒー酸）、フェルラ酸、イソフェルラ酸、シナピン酸、シリンガ酸、デヒドロキナ酸、デヒドロシキミ酸、シキミ酸、コリスミ酸、Ｌ－トリプトファン、Ｌ－チロシン、プレフェン酸、アロゲン酸、Ｌ－フェニルアラニン等が挙げられる。 Specific examples of the cyclic compound include benzoic acid, phthalic acid, isophthalic acid, terephthalic acid, hemmellitic acid, trimellitic acid, trimesic acid, melophonic acid, planar acid, pyromellitic acid, phenylacetic acid and hydroxyphenylacetic acid. , Phenylbutyric acid (phenyllactate), hydroxyphenylbutyric acid, phenylpyrvic acid, hydroxyphenylpyrvic acid, phenyllactic acid, hydroxyphenyllactic acid, anthranilic acid, hydroatropic acid, atropic acid, hydrosilicic acid (kumalic acid), silicic acid, salicylic acid (2-Hydroxybenzoic acid), m-salicylic acid (3-hydroxybenzoic acid), p-salicylic acid (4-hydroxybenzoic acid), methoxybenzoic acid, aminobenzoic acid, hydroxybenzoic acid, pyrocatechuic acid (2,3-dihydroxy) Benzoic acid), β-resorcilic acid (2,4-dihydroxybenzoic acid), gentidic acid (2,5-dihydroxybenzoic acid), γ-resorcilic acid (2,6-dihydroxybenzoic acid), protocatechuic acid (3,4) -Dihydroxybenzoic acid), α-resorcilic acid (3,5-dihydroxybenzoic acid), trihydroxybenzoic acid, vanillic acid (4-hydroxy-3-methoxybenzoic acid), isovanic acid (3-hydroxy-4-methoxybenzoic acid) Acids), veratrumic acid, gallic acid, syring acid, asaronic acid, mandelic acid, vanylmandelic acid, anis acid, homoprotocatechuic acid, homovanic acid, homoisovanic acid, homoberatrumic acid, homophthalic acid, homoisophthalic acid, homoterephthalic acid, phthalone. Acids, isophthalonic acid, terephthalonic acid, atrolactinic acid, tropic acid, melirot acid, floret acid, dihydrocaffeic acid, hydroferulic acid, hydroisoferulic acid, umbiliic acid, caffeic acid (coffee acid), ferulic acid, isoferulic acid, Examples thereof include synapic acid, syringic acid, dehydroquinic acid, dehydroshikimic acid, shikimic acid, corismic acid, L-tryptophan, L-tyrosine, prefenic acid, allogenic acid, L-phenylalanine and the like.
　また、環式化合物の別の具体例としては、フラボノイド、リグナン、カルコン、スチルベノイド、アルカロイド、クルクミノイド、テルペノイド、サポニン、各種配糖体、各種ポリフェノール系芳香族化合物のようなポリフェノール類の他、アミノ酸、ビタミン等が挙げられる。 Further, as another specific example of the cyclic compound, flavonoids, lignans, chalcones, stilbenoids, alkaloids, curcuminoids, terpenoids, saponins, various glycosides, polyphenols such as various polyphenol aromatic compounds, as well as amino acids, Examples include vitamins.
　このうち、フラボノイドとしては、例えば、オーランチニジン、シアニジン、デルフィニジン、ヨーロピニジン、ルテオリニジン、ペラルゴニジン、マルビジン、ペオニジン、ペチュニジン、ロシニジンのようなアントシアニジン、プロシアニジンのようなアントシアニン、ナリンゲニン、エリオシトリン、ピノセムブリン、エリオジクチオールのようなフラバノン、カテキンのようなフラバン、アピゲニン、ルテオリン、バイカレイン、クリシンのようなフラボン、ケルセチン、ケンプフェロールのようなフラボノール、イソフラボン、イソフラバン、イソフラバンジオール、ゲニステインのようなイソフラボノイドの他、ネオフラボノイド、ビフラボノイド、オーロン、プレニル化フラボノイド、Ｏ－メチル化フラボノイド等が挙げられる。 Among these, flavonoids include, for example, aurantidin, cyanidin, delphinidin, Europeanidin, luteolinidin, pelargonidin, malvidin, peonidin, petunidin, anthocyanidin such as rosinidin, anthocyanidin such as procyanidin, naringenin, eriocitrin, pinosembrin, Flavanones such as thiol, flavans such as catechin, apigenin, luteolin, baicalene, flavones such as chrycin, quercetin, flavonols such as kempferol, isoflavones, isoflavans, isoflavandiols, isoflavonoids such as genistein, etc. Examples thereof include neo-flavonoids, biflavonoids, aurones, prenyl flavonoids, and O-methylated flavonoids.
　また、リグナンとしては、例えば、ピノレシノール、ラリシレシノール、セコイソラリシレシノール、マタイレシノール、ヒドロキシマタイレシノール、シリンガレシノール、セサミン、アルクチゲニン、セサミノール、ポドフィロトキシン、ステガナシン等が挙げられる。 Examples of lignans include pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, cilingalesinol, sesamin, arctigenin, sesaminol, podophyllotoxin, and steganacin.
　さらに、スチルベノイドとしては、例えば、ピセアタンノール、ピノシルビン、プテロスチルベン、レスベラトロール、４’－メトキシレスベラトロール、ピノスチルベン、ピシアタノールのようなアグリコン、α－ビニフェリン、アンペロプシンＡ、アンペロプシンＥ、ジプトインドネシンＣ－カワン、ジプトインドネシンＦ－ダマールブア、ε－ビニフェリン、フレクスオソールＡ、グネチンＨ、ヘムスレヤノールＤ、ホペアフェノール、ジプトインドネシンＢ、バチカノールＢのようなオリゴマー等が挙げられる。 Further, as stilbenoids, for example, aglycone such as piceatannol, pinosylvin, pterostilbene, resveratrol, 4'-methoxyresveratrol, pinostilbene, pisiatanol, α-biniferin, ampelopsin A, ampelopsin E, diptoindonesi Examples thereof include oligomers such as C-Kawan, Gyptoindonesin F-Damarbua, ε-viniferin, Flexosol A, Gnetin H, Hemsleyanol D, Hopephenol, Dyptoindonesin B, and Vaticanol B.
　また、クルクミノイドとしては、例えば、クルクミン、ショウガオール等が挙げられる。 Examples of curcuminoids include curcumin and ginger.
　さらに、テルペノイドとしては、例えば、ルテイン、ビタミンＡ、ビタミンＥ、βカロテンのようなカロテノイドの他、シトステロールのようなステロイド等が挙げられる。 Furthermore, examples of terpenoids include carotenoids such as lutein, vitamin A, vitamin E, and β-carotene, as well as steroids such as sitosterol.
　また、各種配糖体としては、例えば、サリシン、β－グルコガリン、サリチル酸グルコシド、サリドロシド、ガストロジン、ポプリン、フロリジン、アルブチンのようなフェノール配糖体、エスクリンのようなクマリン配糖体、ヘスペリジン、ルチンのようなフラボノイド配糖体、アストリンギン、ピセイド、ジプトインドネシンＡのようなスチルベノイド配糖体等が挙げられる。 Examples of various glycosides include salicin, β-glucogarin, salicylate glucoside, salidroside, gastrodin, populin, floridine, phenol glycosides such as arbutin, coumarin glycosides such as esculin, hesperidin, and rutin. Flavonoid glycosides such as, astringin, piseide, stilbenoid glycosides such as diptoindonesin A and the like can be mentioned.
　さらに、各種ポリフェノール系芳香族化合物としては、例えば、チロソール、ヒドロキシチロソール、エスクレチン、フロレチン、ロスマリン酸、サルビアン酸Ａ、レチクリン、パラクマリルアルコール、コニフェリルアルコール、カフェイルアルコール等が挙げられる。 Further, examples of various polyphenolic aromatic compounds include tyrosol, hydroxytyrosol, esculetin, phloretin, rosmarinic acid, salbianic acid A, reticrine, paracoumaryl alcohol, coniferyl alcohol, caffeyl alcohol and the like.
　また、アミノ酸としては、例えば、フェニルアラニン、チロシン等が挙げられる。
　さらに、ビタミンとしては、例えば、ビタミンＡ、ビタミンＤ、ビタミンＥ等が挙げられる。 Examples of amino acids include phenylalanine and tyrosine.
Further, examples of the vitamin include vitamin A, vitamin D, vitamin E and the like.
　また、環式化合物のさらに別の具体例としては、芳香族化合物、脂環式化合物、脂肪族化合物、複素環式化合物等が挙げられる。 Further, further specific examples of the cyclic compound include aromatic compounds, alicyclic compounds, aliphatic compounds, heterocyclic compounds and the like.
　このうち、芳香族化合物としては、例えば、バニリン、２－フェニルエタノール、フェニル酢酸、シンナミックアルコール、イソオイゲノール、フェルラ酸、４－アミノ安息香酸、アネトール、エストラゴール、アントラニル酸メチル、桂皮酸メチル、桂皮酸エチル、フェニルアセトアルデヒド、シンナミックアルデヒド、酢酸シンナミル、レゾルシン、４－ビニルフェノール、４－ビニル－２－メトキシフェノール、３，４－ジヒドロキシスチレン、ドーパミン、レボドパ、ハイドロキノン、クマリン、７－ヒドロキシクマリン、４－ヒドロキシクマリン、キシアメンマイシンＡ等が挙げられる。 Among these, examples of aromatic compounds include vanillin, 2-phenylethanol, phenylacetic acid, synamic alcohol, isoeugenol, ferulic acid, 4-aminobenzoic acid, anetol, estragor, methyl anthranilate, and methyl cinnamic acid. Ethyl cinnamate, phenylacetaldehyde, synamic aldehyde, cinnamyl acetate, resorcin, 4-vinylphenol, 4-vinyl-2-methoxyphenol, 3,4-dihydroxystyrene, dopamine, levodopa, hydroquinone, coumarin, 7-hydroxycoumarin, Examples thereof include 4-hydroxycoumarin and xyamenmycin A.
　また、脂環式化合物としては、例えば、カルベオール、ペリラアルコール、ボルネオール、ジャスモン酸メチル、１，８－シネオール、Ｌ－メントン、バレンセン、ヌートカトン、α－ピネン、カンフェン、Ｌ－カルボン、ペリラアルデヒド、ミルテナール、酢酸Ｌ－メンチル、β－イオノン等が挙げられる。 Examples of the alicyclic compound include carveol, perilla alcohol, borneol, methyl jasmonate, 1,8-cineole, L-menthone, valencene, nootkatone, α-pinene, camphene, L-carboxylic, perillaaldehyde, and myltenal. , L-menthyl acetate, β-ionone and the like.
　さらに、脂肪族化合物としては、例えば、シス－３－ヘキセノール、酢酸シス－３－ヘキセニル、アセトイン、ネロール、ファルネソール、アルギニン、ムコン酸等が挙げられる。 Further, examples of the aliphatic compound include cis-3-hexenol, cis-3-hexenyl acetate, acetoin, nerol, farnesol, arginine, muconic acid and the like.
　また、複素環式化合物としては、例えば、ナイアシン、ナイアシンアミド、マルトール、インドール等が挙げられる。このうち、インドールとしては、例えば５，６－ジヒドロキシインドールが挙げられる。 Examples of the heterocyclic compound include niacin, niacinamide, maltol, and indole. Among these, examples of the indole include 5,6-dihydroxyindole.
　一方、環式化合物の誘導体としては、例えば、上述した化合物のエステル、酸無水物、アミド、酸ハロゲン化物、塩等、または、環式化合物から誘導される全ての化合物が挙げられる。 On the other hand, examples of the derivative of the cyclic compound include esters, acid anhydrides, amides, acid halides, salts and the like of the above-mentioned compounds, or all compounds derived from the cyclic compound.
　なお、環式化合物またはその誘導体の分子量は、特に限定されないが、１２０～１０００であるのが好ましく、１３０～８００であるのがより好ましい。 The molecular weight of the cyclic compound or its derivative is not particularly limited, but is preferably 120 to 1000, and more preferably 130 to 800.
　また、上記式（１）で表される環式化合物の環Ａが、環構成原子が全て炭素原子である飽和環または部分飽和環の５員環である場合、Ｒ２～Ｒ５およびＸが結合する環Ａの炭素原子のうち、１つ以上が不斉炭素原子であるのが好ましい。また、上記式（１）で表される環式化合物の環Ａが、環構成原子が全て炭素原子である飽和環または部分飽和環の６員環である場合、Ｒ２～Ｒ６およびＸが結合する環Ａの炭素原子のうち、１つ以上が不斉炭素原子であるのが好ましい。 Also, Ring A cyclic compound represented by the above formula (1) is, when the ring constituent atoms are all 5-membered ring saturated ring or partially saturated ring are carbon atoms, R 2 ~ R 5 and X It is preferable that one or more of the carbon atoms of the ring A to be bonded are asymmetric carbon atoms. Also, Ring A cyclic compound represented by the above formula (1) is, when the ring constituent atoms are all 6-membered ring saturated ring or partially saturated ring are carbon atoms, R 2 ~ R 6 and X It is preferable that one or more of the carbon atoms of the ring A to be bonded are asymmetric carbon atoms.
　このような場合、環式化合物は立体異性体となる。この場合、本実施形態によれば、特定の立体異性体を高純度に含み、かつ、それ以外の立体異性体の含有率が低い環式化合物を高い収率で製造することが可能になる。その結果、不要な立体異性体の除去に伴う複雑な工程が必要なくなるので、製造コストの低コスト化を図ることができる。 In such a case, the cyclic compound becomes a stereoisomer. In this case, according to the present embodiment, it is possible to produce a cyclic compound containing a specific stereoisomer with high purity and having a low content of other stereoisomers in a high yield. As a result, the complicated process associated with the removal of unnecessary stereoisomers is not required, so that the manufacturing cost can be reduced.
　また、上記式（１）で表される環式化合物においてＸが結合する環Ａの炭素原子をＣ１とし、Ｒ２が結合する環Ａの炭素原子をＣ２とし、Ｒ３が結合する環Ａの炭素原子をＣ３とし、Ｒ４が結合する環Ａの炭素原子をＣ４とし、Ｒ５が結合する環Ａの炭素原子をＣ５とし、Ｒ６が結合する環Ａの炭素原子をＣ６としたとき、これらの炭素原子が不斉炭素原子である組み合わせが、下記（ａ）～（ｈ）からなる群から選択される１種であることが好ましい。 Further, in the cyclic compound represented by the above formula (1), the carbon atom of the ring A to which X is bonded is C 1 , the carbon atom of the ring A to which R 2 is bonded is C 2, and the ring to which R 3 is bonded. The carbon atom of A is C 3 , the carbon atom of ring A to which R 4 is bonded is C 4 , the carbon atom of ring A to which R 5 is bonded is C 5, and the carbon atom of ring A to which R 6 is bonded is C 5. when a C 6, a combination of these carbon atoms is an asymmetric carbon atom is preferably one selected from the group consisting of the following (a) ~ (h).
（ａ）Ｃ１
（ｂ）Ｃ２
（ｃ）Ｃ３
（ｄ）Ｃ４
（ｅ）Ｃ１およびＣ４
（ｆ）Ｃ３およびＣ４
（ｇ）Ｃ１、Ｃ３およびＣ４
（ｈ）Ｃ３、Ｃ４およびＣ５ (A) C 1
(B) C 2
(C) C 3
(D) C 4
(E) C 1 and C 4
(F) C 3 and C 4
(G) C 1 , C 3 and C 4
(H) C 3 , C 4 and C 5
　なお、下記式（２）は、上記式（１）で表される環式化合物に対し、上記Ｃ１～Ｃ６の表示を追記した式である。 Incidentally, the following equation (2) based on the cyclic compound represented by the above formula (1) is an expression that adds the display of the C 1 ~ C 6.
Figure JPOXMLDOC01-appb-C000002
 ［式（２）中、環Ａは、飽和環、部分飽和環もしくは芳香環の５員環または飽和環、部分飽和環もしくは芳香環の６員環であり、Ｘは単結合または１つ以上の炭素数を含む結合であり、Ｙは水素原子またはアルキル基、Ｒ２～Ｒ６（環Ａが５員環の場合はＲ２～Ｒ５）は、独立して、水素原子、水酸基、アミノ基、アルコキシ基、カルボキシル基またはカルボニル基である。また、Ｃ１～Ｃ６は、それぞれ、環Ａの環構成原子としての炭素原子である。］
Figure JPOXMLDOC01-appb-C000002
 [In the formula (2), ring A is a 5-membered ring of a saturated ring, a partially saturated ring or an aromatic ring, or a 6-membered ring of a partially saturated ring or an aromatic ring, and X is a single bond or one or more rings. It is a bond containing the number of carbon atoms, Y is a hydrogen atom or an alkyl group, and R 2 to R 6 (R 2 to R 5 when the ring A is a 5-membered ring) are independently hydrogen atoms, hydroxyl groups, and amino groups. , Alkoxy group, carboxyl group or carbonyl group. Further, C 1 to C 6 are carbon atoms as ring constituent atoms of ring A, respectively. ]
　なお、環式化合物およびその誘導体は、上記式（２）で表される化合物であって、特に、３－デヒドロキネート、３－デヒドロシキミ酸、シキミ酸、コリスミ酸またはプレフェン酸であるのが好ましい。これらの化合物は、多くの分野で利用される化合物であって、その構造は以下の式で表される。 The cyclic compound and its derivative are compounds represented by the above formula (2), and in particular, 3-dehydroquinate, 3-dehydroshikimic acid, shikimic acid, chorismic acid or prephenic acid. preferable. These compounds are compounds used in many fields, and their structures are represented by the following formulas.
　・３－デヒドロキネート ・ 3-Dehydrokinate
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
　・３－デヒドロシキミ酸 ・ 3-Dehydroshikimic acid
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
　・シキミ酸 ・ Shikimic acid
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
　・コリスミ酸 ・ Chorismic acid
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006
　・プレフェン酸 ・ Prephenic acid
Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000007
　以上のような環式化合物またはその誘導体の用途としては、特に限定されないが、例えば、香料組成物、化粧料組成物、医薬品、農薬、化学薬品、電気・電子部品用材料、合成繊維、樹脂、食品添加物等の各種化成品が挙げられる。また、環式化合物またはその誘導体は、各種化成品の原料としても用いられる。この原料としては、例えば、香料原料、化粧料原料、医薬品原料、農薬原料、化学薬品原料、電気・電子部品用原料、合成繊維原料、樹脂原料、食品添加物原料等が挙げられる。なお、原料とは、化成品の合成に用いられる中間体のことをいう。 The uses of the above cyclic compounds or derivatives thereof are not particularly limited, but for example, fragrance compositions, cosmetic compositions, pharmaceuticals, pesticides, chemicals, materials for electrical and electronic parts, synthetic fibers, resins, etc. Examples include various chemical products such as food additives. The cyclic compound or its derivative is also used as a raw material for various chemical products. Examples of this raw material include fragrance raw materials, cosmetic raw materials, pharmaceutical raw materials, agricultural chemical raw materials, chemical raw materials, electric / electronic parts raw materials, synthetic fiber raw materials, resin raw materials, food additive raw materials and the like. The raw material refers to an intermediate used for the synthesis of chemical products.
　以上、本発明の環式化合物またはその誘導体の製造方法を実施形態に基づいて説明したが、本発明はこれらに限定されない。 The method for producing a cyclic compound or a derivative thereof of the present invention has been described above based on the embodiments, but the present invention is not limited thereto.
　例えば、本発明の環式化合物またはその誘導体の製造方法は、前記実施形態に任意の工程が付加されてもよい。 For example, in the method for producing a cyclic compound or a derivative thereof of the present invention, any step may be added to the above-mentioned embodiment.
　次に、本発明の具体的実施例について説明する。
５．環式化合物の製造
　（実施例１Ａ）
　［１］まず、バイオマスに前処理を施し、混合糖を得た。 Next, specific examples of the present invention will be described.
5. Production of Cyclic Compound (Example 1A)
[1] First, biomass was pretreated to obtain mixed sugar.
　［２］次に、増殖させた形質転換体を、混合糖と反応させ、培養液を得た。得られた培養液を遠心分離し、上清液（原料液体）を得た。原料液体における溶質の濃度は、７質量％であった。また、シキミ酸の純度、すなわち溶質の全質量に対するシキミ酸の質量の割合は４８％であった。 [2] Next, the grown transformant was reacted with a mixed sugar to obtain a culture solution. The obtained culture solution was centrifuged to obtain a supernatant solution (raw material liquid). The concentration of the solute in the raw material liquid was 7% by mass. The purity of shikimic acid, that is, the ratio of the mass of shikimic acid to the total mass of the solute was 48%.
　［３］次に、得られた原料液体を真空乾燥法により乾燥させ、乾燥物を得た（第１乾燥工程）。なお、乾燥条件は、温度６５℃、１時間、圧力０．６７Ｐａ以下である。 [3] Next, the obtained raw material liquid was dried by a vacuum drying method to obtain a dried product (first drying step). The drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
　［４］次に、得られた乾燥物を純水に再溶解し、溶液を得た。なお、再溶解に使用した純水の量は、乾燥物１ｇに対して５ｇとした。 [4] Next, the obtained dried product was redissolved in pure water to obtain a solution. The amount of pure water used for redissolution was 5 g with respect to 1 g of the dried product.
　［５］次に、得られた溶液のｐＨを６．０に調整した。続いて、溶液に活性炭処理を施した（吸着工程）。なお、活性炭は、溶液１００ｇに対して０．４ｇ使用した。続いて、活性炭処理を施した溶液のｐＨを３．０に調整した。 [5] Next, the pH of the obtained solution was adjusted to 6.0. Subsequently, the solution was treated with activated carbon (adsorption step). In addition, 0.4 g of activated carbon was used with respect to 100 g of the solution. Subsequently, the pH of the activated carbon-treated solution was adjusted to 3.0.
　［６］次に、ｐＨを調整した溶液を真空乾燥法により乾燥させ、乾燥物を得た（第２乾燥工程）。なお、乾燥条件は、温度６５℃、１時間、圧力０．６７Ｐａ以下である。 [6] Next, the pH-adjusted solution was dried by a vacuum drying method to obtain a dried product (second drying step). The drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
　［７］次に、乾燥物に固液抽出処理を施し、抽出液を得た。固液抽出用の溶媒には、メタノールを用いた。なお、固液抽出処理の温度は３０℃、時間は２時間、溶媒の量は乾燥物１ｇに対して２０ｇとした。 [7] Next, the dried product was subjected to a solid-liquid extraction treatment to obtain an extract. Methanol was used as the solvent for solid-liquid extraction. The temperature of the solid-liquid extraction treatment was 30 ° C., the time was 2 hours, and the amount of the solvent was 20 g with respect to 1 g of the dried product.
　［８］次に、得られた抽出液に晶析処理を施し、シキミ酸（環式化合物）を析出させた。なお、晶析処理では、抽出液の温度および濃度が準安定領域内に位置するように、温度を操作した。 [8] Next, the obtained extract was subjected to crystallization treatment to precipitate shikimic acid (cyclic compound). In the crystallization treatment, the temperature was controlled so that the temperature and concentration of the extract were located within the metastable region.
　［９］次に、シキミ酸を析出させた抽出液に対し、ろ過による固液分離処理を施した。これにより、シキミ酸の結晶を分離し、エタノールで洗浄後、乾燥させて回収した。 [9] Next, the extract in which shikimic acid was precipitated was subjected to a solid-liquid separation treatment by filtration. As a result, the crystals of shikimic acid were separated, washed with ethanol, dried and recovered.
　（実施例２Ａ～４Ａ）
　第１乾燥工程および第２乾燥工程における加熱温度を表１に示すように変更した以外は、実施例１Ａと同様にしてシキミ酸を回収した。 (Examples 2A-4A)
Shikimic acid was recovered in the same manner as in Example 1A except that the heating temperatures in the first drying step and the second drying step were changed as shown in Table 1.
　（実施例５Ａ）
　吸着工程、第２乾燥工程および抽出工程を省略した以外は、実施例１Ａと同様にしてシキミ酸を回収した。 (Example 5A)
Shikimic acid was recovered in the same manner as in Example 1A except that the adsorption step, the second drying step, and the extraction step were omitted.
　（実施例６Ａ）
　第２乾燥工程を省略するとともに、抽出工程を液液抽出処理に変更した以外は、実施例１Ａと同様にしてシキミ酸を回収した。なお、液液抽出用の溶媒として、１－ブタノールを使用した。また、抽出時の温度は３０℃、抽出時間は２時間とした。また、吸着工程を経た溶液１ｇに対して使用した液液抽出用の溶媒の質量を５ｇとした。 (Example 6A)
Shikimic acid was recovered in the same manner as in Example 1A except that the second drying step was omitted and the extraction step was changed to a liquid-liquid extraction treatment. In addition, 1-butanol was used as a solvent for liquid-liquid extraction. The temperature at the time of extraction was 30 ° C., and the extraction time was 2 hours. Further, the mass of the liquid-liquid extraction solvent used was 5 g with respect to 1 g of the solution that had undergone the adsorption step.
　（実施例７Ａ）
　第２乾燥工程を噴霧乾燥法による乾燥に変更した以外は、実施例１Ａと同様にしてシキミ酸を回収した。 (Example 7A)
Shikimic acid was recovered in the same manner as in Example 1A except that the second drying step was changed to drying by the spray drying method.
　（実施例８Ａ）
　析出工程の晶析処理を濃縮乾固に変更した以外は、実施例７Ａと同様にしてシキミ酸を回収した。 (Example 8A)
Shikimic acid was recovered in the same manner as in Example 7A except that the crystallization treatment in the precipitation step was changed to concentrated dry solid.
　（比較例１Ａ）
　第１乾燥工程および第２乾燥工程をそれぞれ噴霧乾燥法による乾燥に変更した以外は、実施例１Ａと同様にしてシキミ酸を回収した。 (Comparative Example 1A)
Shikimic acid was recovered in the same manner as in Example 1A, except that the first drying step and the second drying step were changed to drying by the spray drying method, respectively.
　（比較例２Ａ）
　晶析処理において、抽出液の温度および濃度が不安定領域を通過するように温度を操作した以外は、比較例１Ａと同様にしてシキミ酸を回収した。 (Comparative Example 2A)
In the crystallization treatment, shikimic acid was recovered in the same manner as in Comparative Example 1A, except that the temperature and concentration of the extract were controlled so as to pass through the unstable region.
　（比較例３Ａ）
　第１乾燥工程および第２乾燥工程において、それぞれ、真空乾燥法における圧力を１０ｋＰａに変更するとともに、析出工程の晶析処理を濃縮乾固に変更した以外は、実施例１Ａと同様にしてシキミ酸を回収した。 (Comparative Example 3A)
In the first drying step and the second drying step, shikimic acid was obtained in the same manner as in Example 1A, except that the pressure in the vacuum drying method was changed to 10 kPa and the crystallization treatment in the precipitation step was changed to concentrated dry solid. Was recovered.
　（比較例４Ａ）
　第１乾燥工程および第２乾燥工程において、それぞれ、真空乾燥法における圧力を０．６７Ｐａに変更するとともに、温度を５５℃に変更した以外は、比較例３Ａと同様にしてシキミ酸を回収した。 (Comparative Example 4A)
In the first drying step and the second drying step, shikimic acid was recovered in the same manner as in Comparative Example 3A, except that the pressure in the vacuum drying method was changed to 0.67 Pa and the temperature was changed to 55 ° C.
　（比較例５Ａ）
　第１乾燥工程および第２乾燥工程において、それぞれ、真空乾燥法における温度を１３０℃に変更した以外は、比較例４Ａと同様にしてシキミ酸を回収した。 (Comparative Example 5A)
In each of the first drying step and the second drying step, shikimic acid was recovered in the same manner as in Comparative Example 4A except that the temperature in the vacuum drying method was changed to 130 ° C.
６．環式化合物の評価
　６．１．純度の算出
　実施例１Ａ～８Ａおよび比較例１Ａ～４Ａにおける析出工程直後の固体について、高速液体クロマトグラフィー（ＨＰＬＣ）により、シキミ酸の純度を測定した。なお、純度は、析出工程直後の固体の全質量に対するシキミ酸の質量の割合（単位：％）とした。 6. Evaluation of cyclic compounds 6.1. Calculation of Purity The purity of shikimic acid was measured by high performance liquid chromatography (HPLC) on the solids immediately after the precipitation step in Examples 1A to 8A and Comparative Examples 1A to 4A. The purity was defined as the ratio of the mass of shikimic acid to the total mass of the solid immediately after the precipitation step (unit:%).
　また、測定条件は、以下の通りである。
　＜シキミ酸のＨＰＬＣ分析条件＞
　カラム：ＣＯＳＭＯＳＩＬ　５Ｃ１８－ＡＲ－ＩＩ（φ４．６ｍｍ×２５０ｍｍ）ナカライテスク社製
　移動相：水／メタノール／過塩素酸＝４／１／０．００７５（ｖｏｌ／ｖｏｌ／ｖｏｌ）イソクラティック溶出
　流量：１ｍＬ／ｍｉｎ
　カラム温度：４０℃
　検出方法：フォトダイオードアレイ（ＰＤＡ）検出器（２１０ｎｍ）
　算出結果を表１に示す。 The measurement conditions are as follows.
<HPLC analysis conditions for shikimic acid>
Column: COSMOSIL 5C18-AR-II (φ4.6 mm × 250 mm) Made by Nacalai Tesque Mobile phase: Water / methanol / perchloric acid = 4/1 / 0.0075 (vol / vol / vol) Isocratic elution flow rate: 1 mL / min
Column temperature: 40 ° C
Detection method: Photodiode array (PDA) detector (210 nm)
The calculation results are shown in Table 1.
　６．２．収率の算出
　実施例１Ａ～８Ａおよび比較例１Ａ～４Ａにおける析出工程直後の固体について、シキミ酸の収率を算出した。シキミ酸の収率の算出にあたっては、まず、原料液体中のシキミ酸の量を高速液体クロマトグラフィー（ＨＰＬＣ）により測定した。次いで、析出工程直後の固体の質量とシキミ酸の純度からシキミ酸の析出量を算出した。そして、原料液体中のシキミ酸の含有量に対する、シキミ酸の析出量の割合（単位：％）を算出し、これをシキミ酸の収率とした。
　測定結果を表１に示す。 6.2. Calculation of Yield The yield of shikimic acid was calculated for the solids immediately after the precipitation step in Examples 1A to 8A and Comparative Examples 1A to 4A. In calculating the yield of shikimic acid, first, the amount of shikimic acid in the raw material liquid was measured by high performance liquid chromatography (HPLC). Next, the amount of shikimic acid precipitated was calculated from the mass of the solid immediately after the precipitation step and the purity of shikimic acid. Then, the ratio (unit:%) of the amount of precipitation of shikimic acid to the content of shikimic acid in the raw material liquid was calculated, and this was used as the yield of shikimic acid.
The measurement results are shown in Table 1.
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
　表１から明らかなように、実施例１Ａ～８Ａでは、真空乾燥法による第１乾燥工程を経ることによって、高い純度の環式化合物を高い収率で析出させることができた。このため、最終的に固液分離工程を経た後も、高い純度の環式化合物を高い収率で回収することができた。 As is clear from Table 1, in Examples 1A to 8A, a high-purity cyclic compound could be precipitated in a high yield by undergoing the first drying step by the vacuum drying method. Therefore, even after the final solid-liquid separation step, a high-purity cyclic compound could be recovered in a high yield.
　なお、シキミ酸に代えて、環式化合物の一例である４－ヒドロキシ安息香酸の製造も行ったが、シキミ酸の場合と同様の傾向が認められた。 In addition, instead of shikimic acid, 4-hydroxybenzoic acid, which is an example of a cyclic compound, was also produced, but the same tendency as in the case of shikimic acid was observed.
７．環式化合物の製造
　（実施例１Ｂ）
　［１］まず、バイオマスに前処理を施し、混合糖を得た。 7. Production of Cyclic Compound (Example 1B)
[1] First, biomass was pretreated to obtain mixed sugar.
　［２］次に、増殖させた形質転換体を、混合糖と反応させ、培養液を得た。得られた培養液を遠心分離し、上清液（原料液体）を得た。原料液体における溶質の濃度は、７質量％であった。また、シキミ酸の純度、すなわち溶質の全質量に対するシキミ酸の質量の割合は４８％であった。 [2] Next, the grown transformant was reacted with a mixed sugar to obtain a culture solution. The obtained culture solution was centrifuged to obtain a supernatant solution (raw material liquid). The concentration of the solute in the raw material liquid was 7% by mass. The purity of shikimic acid, that is, the ratio of the mass of shikimic acid to the total mass of the solute was 48%.
　［３］次に、得られた原料液体を真空乾燥法により乾燥させ、乾燥物を得た（第１乾燥工程）。なお、乾燥条件は、温度６５℃、１時間、圧力０．６７Ｐａ以下である。 [3] Next, the obtained raw material liquid was dried by a vacuum drying method to obtain a dried product (first drying step). The drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
　［４］次に、得られた乾燥物を純水に再溶解し、第１溶液を得た。なお、再溶解に使用した純水の量は、乾燥物１ｇに対して５ｇとした。 [4] Next, the obtained dried product was redissolved in pure water to obtain a first solution. The amount of pure water used for redissolution was 5 g with respect to 1 g of the dried product.
　［５］次に、得られた第１溶液のｐＨを６．０に調整し、これにより、第１溶液において化合物の存在量がイオンの存在量よりも少なくなるようにした。続いて、第１溶液に活性炭処理を施した（吸着工程）。なお、活性炭は、第１溶液１００ｇに対して０．４ｇ使用した。続いて、活性炭処理を施した第２溶液のｐＨを３．０に調整し、これにより、第２溶液において化合物の存在量がイオンの存在量以上になるようにした。 [5] Next, the pH of the obtained first solution was adjusted to 6.0 so that the abundance of the compound in the first solution was smaller than the abundance of ions. Subsequently, the first solution was treated with activated carbon (adsorption step). In addition, 0.4 g of activated carbon was used with respect to 100 g of the first solution. Subsequently, the pH of the second solution treated with activated carbon was adjusted to 3.0 so that the abundance of the compound in the second solution was equal to or greater than the abundance of ions.
　［６］次に、ｐＨを調整した第２溶液を真空乾燥法により乾燥させ、乾燥物を得た（第２乾燥工程）。なお、乾燥条件は、温度６５℃、１時間、圧力０．６７Ｐａ以下である。 [6] Next, the pH-adjusted second solution was dried by a vacuum drying method to obtain a dried product (second drying step). The drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
　［７］次に、乾燥物に固液抽出処理を施し、抽出液を得た。固液抽出用の溶媒には、メタノールを用いた。なお、固液抽出処理の温度は３０℃、時間は２時間、溶媒の量は乾燥物１ｇに対して２０ｇとした。 [7] Next, the dried product was subjected to a solid-liquid extraction treatment to obtain an extract. Methanol was used as the solvent for solid-liquid extraction. The temperature of the solid-liquid extraction treatment was 30 ° C., the time was 2 hours, and the amount of the solvent was 20 g with respect to 1 g of the dried product.
　［８］次に、得られた抽出液に晶析処理を施し、シキミ酸（環式化合物）を析出させた。なお、晶析処理では、抽出液の温度および濃度が準安定領域内に位置するように、温度を操作した。 [8] Next, the obtained extract was subjected to crystallization treatment to precipitate shikimic acid (cyclic compound). In the crystallization treatment, the temperature was controlled so that the temperature and concentration of the extract were located within the metastable region.
　［９］次に、シキミ酸を析出させた抽出液に対し、ろ過による固液分離処理を施した。これにより、シキミ酸の結晶を分離し、エタノールで洗浄後、乾燥させて回収した。 [9] Next, the extract in which shikimic acid was precipitated was subjected to a solid-liquid separation treatment by filtration. As a result, the crystals of shikimic acid were separated, washed with ethanol, dried and recovered.
　（実施例２Ｂ～４Ｂ）
　第１乾燥工程および第２乾燥工程における加熱温度を表２に示すように変更した以外は、実施例１Ｂと同様にしてシキミ酸を回収した。 (Examples 2B to 4B)
Shikimic acid was recovered in the same manner as in Example 1B except that the heating temperatures in the first drying step and the second drying step were changed as shown in Table 2.
　（実施例５Ｂ）
　第２乾燥工程を省略するとともに、抽出工程を液液抽出処理に変更した以外は、実施例１Ｂと同様にしてシキミ酸を回収した。なお、液液抽出用の溶媒として、１－ブタノールを使用した。また、抽出時の温度は３０℃、抽出時間は２時間とした。また、吸着工程を経た溶液１ｇに対して使用した液液抽出用の溶媒の質量を５ｇとした。 (Example 5B)
Shikimic acid was recovered in the same manner as in Example 1B except that the second drying step was omitted and the extraction step was changed to a liquid-liquid extraction treatment. In addition, 1-butanol was used as a solvent for liquid-liquid extraction. The temperature at the time of extraction was 30 ° C., and the extraction time was 2 hours. Further, the mass of the liquid-liquid extraction solvent used was 5 g with respect to 1 g of the solution that had undergone the adsorption step.
　（実施例６Ｂ、７Ｂ）
　吸着工程における第１溶液のｐＨおよび第２溶液のｐＨをそれぞれ表２に示すように変更した以外は、実施例３Ｂと同様にしてシキミ酸を回収した。 (Examples 6B and 7B)
Shikimic acid was recovered in the same manner as in Example 3B, except that the pH of the first solution and the pH of the second solution in the adsorption step were changed as shown in Table 2, respectively.
　（実施例８Ｂ）
　第２乾燥工程を噴霧乾燥法による乾燥に変更した以外は、実施例１Ｂと同様にしてシキミ酸を回収した。 (Example 8B)
Shikimic acid was recovered in the same manner as in Example 1B except that the second drying step was changed to drying by the spray drying method.
　（比較例１Ｂ）
　第１乾燥工程および第２乾燥工程をそれぞれ噴霧乾燥法による乾燥に変更するとともに、吸着工程における第１溶液のｐＨおよび第２溶液のｐＨをそれぞれ表２に示すように変更した以外は、実施例１Ｂと同様にしてシキミ酸を回収した。 (Comparative Example 1B)
Examples except that the first drying step and the second drying step were changed to drying by the spray drying method, and the pH of the first solution and the pH of the second solution in the adsorption step were changed as shown in Table 2, respectively. Sikimic acid was recovered in the same manner as in 1B.
　（比較例２Ｂ）
　晶析処理において、抽出液の温度および濃度が不安定領域を通過するように温度を操作した以外は、比較例１Ｂと同様にしてシキミ酸を回収した。 (Comparative Example 2B)
In the crystallization treatment, shikimic acid was recovered in the same manner as in Comparative Example 1B, except that the temperature and concentration of the extract were controlled so as to pass through the unstable region.
　（比較例３Ｂ、４Ｂ）
　吸着工程における第１溶液のｐＨおよび第２溶液のｐＨをそれぞれ表２に示すように変更した以外は、実施例９Ｂと同様にしてシキミ酸を回収した。 (Comparative Examples 3B and 4B)
Shikimic acid was recovered in the same manner as in Example 9B, except that the pH of the first solution and the pH of the second solution in the adsorption step were changed as shown in Table 2, respectively.
８．環式化合物の評価
　８．１．純度の算出
　実施例１Ｂ～８Ｂおよび比較例１Ｂ～４Ｂにおける析出工程直後の固体について、高速液体クロマトグラフィー（ＨＰＬＣ）により、シキミ酸の純度を測定した。なお、純度は、析出工程直後の固体の全質量に対するシキミ酸の質量の割合（単位：％）とした。
　また、測定条件は、以下の通りである。 8. Evaluation of cyclic compounds 8.1. Calculation of Purity The purity of shikimic acid was measured by high performance liquid chromatography (HPLC) on the solids immediately after the precipitation step in Examples 1B to 8B and Comparative Examples 1B to 4B. The purity was defined as the ratio of the mass of shikimic acid to the total mass of the solid immediately after the precipitation step (unit:%).
The measurement conditions are as follows.
　＜シキミ酸のＨＰＬＣ分析条件＞
　カラム：ＣＯＳＭＯＳＩＬ　５Ｃ１８－ＡＲ－ＩＩ（φ４．６ｍｍ×２５０ｍｍ）ナカライテスク社製
　移動相：水／メタノール／過塩素酸＝４／１／０．００７５（ｖｏｌ／ｖｏｌ／ｖｏｌ）イソクラティック溶出
　流量：１ｍＬ／ｍｉｎ
　カラム温度：４０℃
　検出方法：フォトダイオードアレイ（ＰＤＡ）検出器（２１０ｎｍ）
　算出結果を表２に示す。 <HPLC analysis conditions for shikimic acid>
Column: COSMOSIL 5C18-AR-II (φ4.6 mm × 250 mm) Made by Nacalai Tesque Mobile phase: Water / methanol / perchloric acid = 4/1 / 0.0075 (vol / vol / vol) Isocratic elution flow rate: 1 mL / min
Column temperature: 40 ° C
Detection method: Photodiode array (PDA) detector (210 nm)
The calculation results are shown in Table 2.
　８．２．収率の算出
　実施例１Ｂ～８Ｂおよび比較例１Ｂ～４Ｂにおける析出工程直後の固体について、シキミ酸の収率を算出した。シキミ酸の収率の算出にあたっては、まず、原料液体中のシキミ酸の量を高速液体クロマトグラフィー（ＨＰＬＣ）により測定した。次いで、析出工程直後の固体の質量とシキミ酸の純度からシキミ酸の析出量を算出した。そして、原料液体中のシキミ酸の含有量に対する、シキミ酸の析出量の割合（単位：％）を算出し、これをシキミ酸の収率とした。
　測定結果を表２に示す。 8.2. Calculation of Yield The yield of shikimic acid was calculated for the solids immediately after the precipitation step in Examples 1B to 8B and Comparative Examples 1B to 4B. In calculating the yield of shikimic acid, first, the amount of shikimic acid in the raw material liquid was measured by high performance liquid chromatography (HPLC). Next, the amount of shikimic acid precipitated was calculated from the mass of the solid immediately after the precipitation step and the purity of shikimic acid. Then, the ratio (unit:%) of the amount of precipitation of shikimic acid to the content of shikimic acid in the raw material liquid was calculated, and this was used as the yield of shikimic acid.
The measurement results are shown in Table 2.
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
　表２から明らかなように、吸着工程における第１溶液中の環式化合物の存在量およびイオンの存在量の大小関係に関し、実施例１Ｂ～８Ｂでは、これらを最適化することによって、高い純度の環式化合物を高い収率で析出させることができた。このため、最終的に固液分離工程を経た後も、高い純度の環式化合物を高い収率で回収することができた。 As is clear from Table 2, regarding the magnitude relationship between the abundance of the cyclic compound and the abundance of ions in the first solution in the adsorption step, in Examples 1B to 8B, high purity was achieved by optimizing these. The cyclic compound could be precipitated in high yield. Therefore, even after the final solid-liquid separation step, a high-purity cyclic compound could be recovered in a high yield.
　なお、シキミ酸に代えて、環式化合物の一例である４－ヒドロキシ安息香酸の製造も行ったが、シキミ酸の場合と同様の傾向が認められた。 In addition, instead of shikimic acid, 4-hydroxybenzoic acid, which is an example of a cyclic compound, was also produced, but the same tendency as in the case of shikimic acid was observed.
９．環式化合物の製造
　（実施例１Ｃ）
　［１］まず、バイオマスに前処理を施し、混合糖を得た。 9. Production of Cyclic Compound (Example 1C)
[1] First, biomass was pretreated to obtain mixed sugar.
　［２］次に、増殖させた形質転換体を、混合糖と反応させ、培養液を得た。得られた培養液を遠心分離し、上清液（原料液体）を得た。原料液体における溶質の濃度は、７質量％であった。また、シキミ酸の純度、すなわち溶質の全質量に対するシキミ酸の質量の割合は４８％であった。 [2] Next, the grown transformant was reacted with a mixed sugar to obtain a culture solution. The obtained culture solution was centrifuged to obtain a supernatant solution (raw material liquid). The concentration of the solute in the raw material liquid was 7% by mass. The purity of shikimic acid, that is, the ratio of the mass of shikimic acid to the total mass of the solute was 48%.
　［３］次に、得られた原料液体を真空乾燥法により乾燥させ、乾燥物を得た（第１乾燥工程）。なお、乾燥条件は、温度６５℃、１時間、圧力０．６７Ｐａ以下である。 [3] Next, the obtained raw material liquid was dried by a vacuum drying method to obtain a dried product (first drying step). The drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
　［４］次に、得られた乾燥物を純水に再溶解し、溶液を得た。なお、再溶解に使用した純水の量は、乾燥物１ｇに対して５ｇとした。 [4] Next, the obtained dried product was redissolved in pure water to obtain a solution. The amount of pure water used for redissolution was 5 g with respect to 1 g of the dried product.
　［５］次に、得られた溶液のｐＨを６．０に調整した。続いて、溶液に活性炭処理を施した（吸着工程）。なお、活性炭は、溶液１００ｇに対して０．４ｇ使用した。続いて、活性炭処理を施した溶液のｐＨを３．０に調整した。 [5] Next, the pH of the obtained solution was adjusted to 6.0. Subsequently, the solution was treated with activated carbon (adsorption step). In addition, 0.4 g of activated carbon was used with respect to 100 g of the solution. Subsequently, the pH of the activated carbon-treated solution was adjusted to 3.0.
　［６］次に、ｐＨを調整した溶液を真空乾燥法により乾燥させ、乾燥物を得た（第２乾燥工程）。なお、乾燥条件は、温度６５℃、１時間、圧力０．６７Ｐａ以下である。 [6] Next, the pH-adjusted solution was dried by a vacuum drying method to obtain a dried product (second drying step). The drying conditions are a temperature of 65 ° C. for 1 hour and a pressure of 0.67 Pa or less.
　［７］次に、乾燥物に固液抽出処理を施し、抽出液を得た。固液抽出用の溶媒には、メタノールを用いた。なお、固液抽出処理の温度は３０℃、時間は２時間、溶媒の量は乾燥物１ｇに対して２０ｇとした。 [7] Next, the dried product was subjected to a solid-liquid extraction treatment to obtain an extract. Methanol was used as the solvent for solid-liquid extraction. The temperature of the solid-liquid extraction treatment was 30 ° C., the time was 2 hours, and the amount of the solvent was 20 g with respect to 1 g of the dried product.
　［８］次に、得られた抽出液に晶析処理を施し、シキミ酸（環式化合物）を析出させた。晶析処理では、図４に示す状態Ｃ１から状態Ｃ８に至るまで、抽出液の温度を変化させる操作と、抽出液を撹拌する操作と、を繰り返す処理を施した。すなわち、抽出液における温度および環式化合物の濃度が図４に示す準安定領域内に位置するように、温度を操作した。 [8] Next, the obtained extract was subjected to crystallization treatment to precipitate shikimic acid (cyclic compound). In the crystallization treatment, the operation of changing the temperature of the extract and the operation of stirring the extract were repeated from the state C1 to the state C8 shown in FIG. That is, the temperature was manipulated so that the temperature and the concentration of the cyclic compound in the extract were located within the metastable region shown in FIG.
　［９］次に、シキミ酸を析出させた抽出液に対し、ろ過による固液分離処理を施した。これにより、シキミ酸の結晶を分離し、エタノールで洗浄後、乾燥させて回収した。 [9] Next, the extract in which shikimic acid was precipitated was subjected to a solid-liquid separation treatment by filtration. As a result, the crystals of shikimic acid were separated, washed with ethanol, dried and recovered.
　（実施例２Ｃ）
　前述した実施例１Ｃでは、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を３回ずつ繰り返したのに対し、本実施例２Ｃでは、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を２回ずつ繰り返すようにした以外は、実施例１Ｃと同様にしてシキミ酸を回収した。 (Example 2C)
In Example 1C described above, the operation of lowering the temperature of the extract and the operation of stirring the extract were repeated three times each, whereas in Example 2C, the operation of lowering the temperature of the extract was performed. , The operation of stirring the extract was repeated twice each, and shikimic acid was recovered in the same manner as in Example 1C.
　（実施例３Ｃ）
　前述した実施例１Ｃでは、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を３回ずつ繰り返したのに対し、本実施例３Ｃでは、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を５回ずつ繰り返すようにした以外は、実施例１Ｃと同様にしてシキミ酸を回収した。 (Example 3C)
In Example 1C described above, the operation of lowering the temperature of the extract and the operation of stirring the extract were repeated three times each, whereas in Example 3C, the operation of lowering the temperature of the extract was performed. , The operation of stirring the extract was repeated 5 times each, and shikimic acid was recovered in the same manner as in Example 1C.
　（実施例４Ｃ～８Ｃ）
　第１乾燥工程における加熱温度を表３に示すように変更した以外は、実施例１Ｃと同様にしてシキミ酸を回収した。 (Examples 4C to 8C)
Shikimic acid was recovered in the same manner as in Example 1C except that the heating temperature in the first drying step was changed as shown in Table 3.
　（実施例９Ｃ）
　吸着工程、第２乾燥工程および抽出工程を省略した以外は、実施例１Ｃと同様にしてシキミ酸を回収した。 (Example 9C)
Shikimic acid was recovered in the same manner as in Example 1C except that the adsorption step, the second drying step, and the extraction step were omitted.
　（実施例１０Ｃ）
　第２乾燥工程を省略するとともに、抽出工程を液液抽出処理に変更した以外は、実施例１Ｃと同様にしてシキミ酸を回収した。なお、液液抽出用の溶媒として、１－ブタノールを使用した。また、抽出時の温度は３０℃、抽出時間は２時間とした。また、吸着工程を経た溶液１ｇに対して使用した液液抽出用の溶媒の質量を５ｇとした。 (Example 10C)
Shikimic acid was recovered in the same manner as in Example 1C except that the second drying step was omitted and the extraction step was changed to a liquid-liquid extraction treatment. In addition, 1-butanol was used as a solvent for liquid-liquid extraction. The temperature at the time of extraction was 30 ° C., and the extraction time was 2 hours. Further, the mass of the liquid-liquid extraction solvent used was 5 g with respect to 1 g of the solution that had undergone the adsorption step.
　（実施例１１Ｃ）
　第２乾燥工程を噴霧乾燥法による乾燥に変更した以外は、実施例１Ｃと同様にしてシキミ酸を回収した。 (Example 11C)
Shikimic acid was recovered in the same manner as in Example 1C except that the second drying step was changed to drying by the spray drying method.
　（比較例）
　晶析処理において、図５に示す状態Ｃ９から状態Ｃ１２に至るまでの経路で、抽出液の温度を変化させる操作と、抽出液を撹拌する操作と、を行った以外は、実施例１０Ｃと同様にしてシキミ酸を回収した。 (Comparison example)
In the crystallization treatment, the same as in Example 10C except that the operation of changing the temperature of the extract and the operation of stirring the extract were performed in the path from the state C9 to the state C12 shown in FIG. The shikimic acid was recovered.
　図５は、比較例に係る晶析処理を説明するための図であって、横軸に抽出液の温度、縦軸に抽出液における環式化合物の溶解度をとったとき、これらの間の関係を示す図である。なお、図５に示す状態Ｃ９から状態Ｃ１２までの各状態のうち、状態Ｃ９、状態Ｃ１０および状態Ｃ１２は、準安定領域内に位置しているが、状態Ｃ１１は、不安定領域内に位置している。したがって、図５と前述した図４とでは、不安定領域内に位置する状態があるか否かの差異がある。 FIG. 5 is a diagram for explaining the crystallization treatment according to the comparative example, and when the horizontal axis represents the temperature of the extract and the vertical axis represents the solubility of the cyclic compound in the extract, the relationship between them. It is a figure which shows. Of the states C9 to C12 shown in FIG. 5, the states C9, C10 and C12 are located in the metastable region, but the state C11 is located in the unstable region. ing. Therefore, there is a difference between FIG. 5 and FIG. 4 described above as to whether or not there is a state located in the unstable region.
１０．環式化合物の評価
　１０．１．純度の算出
　実施例１Ｃ～１１Ｃおよび比較例における晶析工程直後の固体について、高速液体クロマトグラフィー（ＨＰＬＣ）により、シキミ酸の純度を測定した。なお、純度は、晶析工程直後の固体の全質量に対するシキミ酸の質量の割合（単位：％）とした。
　また、測定条件は、以下の通りである。 10. Evaluation of cyclic compounds 10.1. Calculation of Purity The purity of shikimic acid was measured by high performance liquid chromatography (HPLC) on the solids immediately after the crystallization step in Examples 1C to 11C and Comparative Examples. The purity was defined as the ratio of the mass of shikimic acid to the total mass of the solid immediately after the crystallization step (unit:%).
The measurement conditions are as follows.
　＜シキミ酸のＨＰＬＣ分析条件＞
　カラム：ＣＯＳＭＯＳＩＬ　５Ｃ１８－ＡＲ－ＩＩ（φ４．６ｍｍ×２５０ｍｍ）ナカライテスク社製
　移動相：水／メタノール／過塩素酸＝４／１／０．００７５（ｖｏｌ／ｖｏｌ／ｖｏｌ）イソクラティック溶出
　流量：１ｍＬ／ｍｉｎ
　カラム温度：４０℃
　検出方法：フォトダイオードアレイ（ＰＤＡ）検出器（２１０ｎｍ）
　算出結果を表３に示す。 <HPLC analysis conditions for shikimic acid>
Column: COSMOSIL 5C18-AR-II (φ4.6 mm × 250 mm) Made by Nacalai Tesque Mobile phase: Water / methanol / perchloric acid = 4/1 / 0.0075 (vol / vol / vol) Isocratic elution flow rate: 1 mL / min
Column temperature: 40 ° C
Detection method: Photodiode array (PDA) detector (210 nm)
The calculation results are shown in Table 3.
　１０．２．収率の算出
　実施例１Ｃ～１１Ｃおよび比較例における晶析工程直後の固体について、シキミ酸の収率を算出した。シキミ酸の収率の算出にあたっては、まず、原料液体中のシキミ酸の量を高速液体クロマトグラフィー（ＨＰＬＣ）により測定した。次いで、晶析工程直後の固体の質量とシキミ酸の純度からシキミ酸の析出量を算出した。そして、原料液体中のシキミ酸の含有量に対する、シキミ酸の析出量の割合（単位：％）を算出し、これをシキミ酸の収率とした。
　測定結果を表３に示す。 10.2. Calculation of Yield The yield of shikimic acid was calculated for the solids immediately after the crystallization step in Examples 1C to 11C and Comparative Examples. In calculating the yield of shikimic acid, first, the amount of shikimic acid in the raw material liquid was measured by high performance liquid chromatography (HPLC). Next, the amount of shikimic acid precipitated was calculated from the mass of the solid immediately after the crystallization step and the purity of shikimic acid. Then, the ratio (unit:%) of the amount of precipitation of shikimic acid to the content of shikimic acid in the raw material liquid was calculated, and this was used as the yield of shikimic acid.
The measurement results are shown in Table 3.
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
　表３から明らかなように、実施例１Ｃ～１１Ｃでは、高い純度の環式化合物を高い収率で析出させることができた。このため、最終的に固液分離工程を経た後も、高い純度の環式化合物を高い収率で回収することができる。特に、晶析処理において、抽出液の温度を低下させる操作と、抽出液を撹拌する操作と、を３回以上ずつ繰り返すことにより、収率を高めることができた。 As is clear from Table 3, in Examples 1C to 11C, a high-purity cyclic compound could be precipitated in a high yield. Therefore, even after the final solid-liquid separation step, a high-purity cyclic compound can be recovered in a high yield. In particular, in the crystallization treatment, the yield could be increased by repeating the operation of lowering the temperature of the extract and the operation of stirring the extract three times or more.
　なお、シキミ酸に代えて、環式化合物の一例である４－ヒドロキシ安息香酸の製造も行ったが、シキミ酸の場合と同様の傾向が認められた。 In addition, instead of shikimic acid, 4-hydroxybenzoic acid, which is an example of a cyclic compound, was also produced, but the same tendency as in the case of shikimic acid was observed.
　本発明の好適な実施形態によれば、適度な温度範囲で加熱する真空乾燥法を用いた第１乾燥工程を有しているため、最終的に高純度な環式化合物を高い収率で回収することができる。また、第１乾燥工程、抽出工程および析出工程を経ることで、不純物となる有機成分および無機成分を順次除去することができ、かかる観点でも、高純度化および高収率化を図ることができる。さらに、得られる環式化合物の白色度を高めることもできる。また、真空乾燥法では、特に短時間での乾燥処理が可能であり、かつ、抽出および析出を利用することによって、環式化合物の取り出しに要するエネルギーの削減が可能になる。その結果、高純度の環式化合物またはその誘導体を高い収率で製造することができる。したがって、本発明は、産業上の利用可能性を有する。 According to a preferred embodiment of the present invention, since the first drying step using a vacuum drying method of heating in an appropriate temperature range is provided, a high-purity cyclic compound is finally recovered in a high yield. can do. Further, by passing through the first drying step, the extraction step and the precipitation step, the organic component and the inorganic component which are impurities can be sequentially removed, and from this viewpoint as well, high purity and high yield can be achieved. .. Furthermore, the whiteness of the obtained cyclic compound can be increased. Further, in the vacuum drying method, the drying treatment can be performed in a particularly short time, and the energy required for extracting the cyclic compound can be reduced by utilizing extraction and precipitation. As a result, a high-purity cyclic compound or a derivative thereof can be produced in a high yield. Therefore, the present invention has industrial applicability.

Claims (11)

  1. 　環式化合物またはその誘導体を含有する原料液体に乾燥処理を施し、乾燥物を得る乾燥工程と、
    　前記乾燥物から前記環式化合物またはその誘導体を抽出用溶媒に抽出し、抽出液を得る抽出工程と、
    　前記抽出液から前記環式化合物またはその誘導体を析出させる析出工程と、
    を有し、
    　前記乾燥処理は、圧力１０Ｐａ以下において前記原料液体を温度６５～１２５℃で加熱する処理であることを特徴とする環式化合物またはその誘導体の製造方法。     A drying step of subjecting a raw material liquid containing a cyclic compound or a derivative thereof to a drying treatment to obtain a dried product, and
    An extraction step of extracting the cyclic compound or a derivative thereof from the dried product into an extraction solvent to obtain an extract, and
    A precipitation step of precipitating the cyclic compound or its derivative from the extract, and
    Have,
    A method for producing a cyclic compound or a derivative thereof, wherein the drying treatment is a treatment of heating the raw material liquid at a temperature of 65 to 125 ° C. at a pressure of 10 Pa or less.
  2. 　前記乾燥工程と前記抽出工程との間に設けられ、前記乾燥物を再溶解用溶媒に溶解させ、再溶解液を調製する再溶解工程と、
    　前記再溶解工程と前記抽出工程との間に設けられ、前記再溶解液に吸着処理を施す吸着工程と、
    をさらに有する請求項１に記載の環式化合物またはその誘導体の製造方法。     A redissolving step provided between the drying step and the extraction step, in which the dried product is dissolved in a solvent for redissolving to prepare a redissolving solution, and
    An adsorption step provided between the redissolving step and the extraction step and adsorbing the redissolving liquid, and an adsorption step.
    The method for producing a cyclic compound or a derivative thereof according to claim 1.
  3. 　環式化合物またはその誘導体を含有する原料液体に乾燥処理を施し、乾燥物を得る乾燥工程と、
    　前記乾燥物を第１溶媒に再溶解し、第１溶液を得る再溶解工程と、
    　前記第１溶液に対し、吸着体への吸着処理を施すことにより、第２溶液を得る吸着工程と、
    　前記第２溶液から前記環式化合物またはその誘導体を析出させる析出工程と、
    を有し、
    　前記第１溶液における前記環式化合物またはその誘導体の存在量が、前記環式化合物またはその誘導体のイオンの存在量よりも少なくなるように、前記第１溶液を調製することを特徴とする環式化合物またはその誘導体の製造方法。     A drying step of subjecting a raw material liquid containing a cyclic compound or a derivative thereof to a drying treatment to obtain a dried product, and
    A re-dissolution step of redissolving the dried product in a first solvent to obtain a first solution, and
    An adsorption step of obtaining a second solution by subjecting the first solution to an adsorbent treatment.
    A precipitation step of precipitating the cyclic compound or its derivative from the second solution, and
    Have,
    The first solution is prepared so that the abundance of the cyclic compound or its derivative in the first solution is smaller than the abundance of ions of the cyclic compound or its derivative. A method for producing a compound or a derivative thereof.
  4. 　前記第２溶液における前記環式化合物またはその誘導体の存在量が、前記環式化合物またはその誘導体のイオンの存在量以上になるように、前記第２溶液を調製する請求項３に記載の環式化合物またはその誘導体の製造方法。 The cyclic formula according to claim 3, wherein the second solution is prepared so that the abundance of the cyclic compound or its derivative in the second solution is equal to or greater than the abundance of ions of the cyclic compound or its derivative. A method for producing a compound or a derivative thereof.
  5. 　前記第１溶液のｐＨが前記第２溶液のｐＨより大きくなるように、前記第１溶液および前記第２溶液を調製する請求項３または４に記載の環式化合物またはその誘導体の製造方法。 The method for producing a cyclic compound or a derivative thereof according to claim 3 or 4, wherein the first solution and the second solution are prepared so that the pH of the first solution is higher than the pH of the second solution.
  6. 　前記乾燥工程の前に設けられ、バイオマスから前記原料液体を調製する原料液体調製工程をさらに有する請求項１ないし５のいずれか１項に記載の環式化合物またはその誘導体の製造方法。 The method for producing a cyclic compound or a derivative thereof according to any one of claims 1 to 5, further comprising a raw material liquid preparation step for preparing the raw material liquid from biomass, which is provided before the drying step.
  7. 　前記原料液体調製工程は、前記原料液体を濃縮する濃縮処理を含む請求項６に記載の環式化合物またはその誘導体の製造方法。 The method for producing a cyclic compound or a derivative thereof according to claim 6, wherein the raw material liquid preparation step includes a concentration treatment for concentrating the raw material liquid.
  8. 　環式化合物またはその誘導体と溶媒とを含有する原料液体の温度を操作する晶析処理により、前記原料液体から前記環式化合物またはその誘導体を析出させる晶析工程を有し、
    　前記晶析処理は、前記原料液体における前記環式化合物またはその誘導体の濃度が準安定領域に位置するように、前記原料液体の温度を操作する処理であることを特徴とする環式化合物またはその誘導体の製造方法。     It has a crystallization step of precipitating the cyclic compound or its derivative from the raw material liquid by a crystallization treatment for controlling the temperature of the raw material liquid containing the cyclic compound or its derivative and a solvent.
    The crystallization treatment is a treatment for controlling the temperature of the raw material liquid so that the concentration of the cyclic compound or its derivative in the raw material liquid is located in the semi-stable region. Derivative manufacturing method.
  9. 　前記晶析処理は、前記原料液体に、前記環式化合物またはその誘導体の種晶を添加する操作を含む請求項８に記載の環式化合物またはその誘導体の製造方法。 The method for producing a cyclic compound or a derivative thereof according to claim 8, wherein the crystallization treatment includes an operation of adding a seed crystal of the cyclic compound or a derivative thereof to the raw material liquid.
  10. 　前記晶析処理は、前記原料液体の温度を低下させる操作と、前記原料液体を撹拌する操作と、を含む請求項８または９に記載の環式化合物またはその誘導体の製造方法。 The method for producing a cyclic compound or a derivative thereof according to claim 8 or 9, wherein the crystallization treatment includes an operation of lowering the temperature of the raw material liquid and an operation of stirring the raw material liquid.
  11. 　バイオマスから前記原料液体を調製する原料液体調製工程をさらに有する請求項８ないし１０のいずれか１項に記載の環式化合物またはその誘導体の製造方法。 The method for producing a cyclic compound or a derivative thereof according to any one of claims 8 to 10, further comprising a raw material liquid preparation step for preparing the raw material liquid from biomass.
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