JP2004216370A - Method and apparatus for crystallization - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for crystallization which realizes production of a crystal having an average particle diameter larger than before, in a so-called neutralization crystallization method. <P>SOLUTION: The method for crystallization comprises: introducing a raw material solution of an organic acid salt to a reaction vessel 2 as a raw solution for reaction; supplying an acid to the raw material solution of the organic acid salt from a dropping tube 10 to thereby once precipitate a desired organic acid crystal; supplying a base into the reaction vessel 2 from another dropping tube 15 to dissolve a part of the precipitated crystal; and further supplying an acid from the dropping tube 10 to crystallize the organic acid. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

  The present invention relates to a method for crystallizing an organic acid, which comprises crystallizing an organic acid by adding an acid to a solution of an organic acid salt, and a crystallizer suitable for the method.

  Generally, the crystallization of an organic acid that is hardly soluble or insoluble in water, such as a carboxylic acid, is called so-called neutralization crystallization, in which a salt thereof is crystallized by reacting with an acid in the presence of water. The reaction is carried out by crystallization.

  As such neutralization crystallization, for example, a method of producing a crystal of an organic acid by adding an acid to an aqueous solution of a water-soluble salt of a crystalline organic acid such as adipic acid or nicotinic acid is known. (For example, see Non-Patent Document 1).

  In the neutralization crystallization method, on the surface of the aqueous alkali solution of the organic compound charged in the container, an acid is dropped using a pump or the like, or in the aqueous alkali solution of the organic compound charged in the container, By dropping an acid using a dip tube, crystals of the organic compound are precipitated.

According to the description of Non-Patent Document 1, when hydrochloric acid is dropped into an aqueous solution of sodium nicotinic acid, first, from the (I) unsaturated state of nicotinic acid, (II) exceeds the saturated solubility of nicotinic acid Through a supersaturated state in which no crystals are precipitated, rapid supersaturation due to (III) crystal precipitation is resolved, and (IV) crystals are precipitated in a saturated state.
Fang Wang et al., “Monitoring pH Swing Crystallization of Notice Acid by the Use of Attenuated Total Reflection Fourier Transform Infrared Spectrometry”, “Ind. Eng. Chem. Res. Vol.39, No.6, 2000”, p.2101 -2104

However, when the present inventors reacted monosodium adipic acid salt with hydrochloric acid by the method described in Non-patent Document 1, the average particle size of the obtained crystals was as small as 129 μm, and the bulk density of the crystals was small. But only crystals of adipic acid as small as 267 kg / m ³ could be obtained.

  As described above, the conventional neutralization crystallization method can only obtain crystals having a small average particle diameter and a small bulk density. For this reason, for example, when filtering out the crystals obtained by crystallization, it is necessary to perform a filtration operation. There is a problem that it takes time.

  The present invention has been made in view of the above problems, and an object of the present invention is to provide a crystallizing method capable of producing a crystal having a larger average particle diameter than the conventional one in a crystallization method called so-called neutralization crystallization. An object of the present invention is to provide an analysis method.

  The inventors of the present application have conducted intensive studies to achieve the above object, and as a result of obtaining only crystals having a small average particle diameter using the above-described conventional neutralization crystallization method, (IV) saturation It was concluded that many new nuclei occurred during the period, especially when the supersaturated state was rapidly resolved by (III) crystal precipitation. That is, as a result of the examination, the present inventors have found that most of the raw material compounds subjected to the crystallization reaction precipitate as nuclei and are hardly used for crystal growth, so that only crystals having a small average particle diameter can be obtained. I came to the idea that I couldn't.

  Thus, the present inventors have conducted further studies to increase the proportion of the compound subjected to crystal growth, and as a result, a part of the fine crystals derived from the nucleus generated by the dropping of the acid is converted into a salt with a base. By dissolving and reacting this salt with an acid again, it was found that the salt can be used for crystal growth.

  In the crystallization method according to the present invention, in the presence of crystals, the pH hardly changes even when an acid or a base is added. This is because, in the crystallization method according to the present invention, the addition of the base only changes the organic acid into a salt, and the addition of the base does not significantly change the pH. For this reason, in the neutralization crystallization in which the crystallization reaction is performed by adding an acid to make the reaction solution at a pH below neutrality, for example, once crystals come out, the pH almost fluctuates even if a base is added. Otherwise, control of such a crystallization reaction seems seemingly impossible. However, the present inventors have found that the above-described reaction occurs by adding a base during crystallization, and further improve the above-described crystallization reaction by controlling the ratio of the acid and the base to be added. Found that it can be controlled. In the present invention, the amount of the acid required for crystallization varies depending on the amount of the base used.

  That is, in order to solve the above problems, the method for crystallizing an organic acid according to the present invention converts a part of the organic acid crystals into an organic acid salt by adding a base to the organic acid crystal-containing liquid and dissolves the organic acid crystals. And adding an acid to the solution of the organic acid salt.

  According to the above configuration, fine crystals can be reduced, and the ratio of the compound used for crystal growth can be increased and crystal growth can be performed efficiently. Has an effect that a large crystal can be stably obtained with good reproducibility.

  Further, in order to solve the above-mentioned problems, the method for crystallizing an organic acid according to the present invention comprises adding an acid to a solution of an organic acid salt to remove at least a part of the organic acid crystals of all the organic acid crystals to be precipitated. By precipitating, by adding a base to the liquid containing the organic acid crystals, a part of the precipitated organic acid crystals is converted into an organic acid salt and dissolved, and an acid is added to a solution of the organic acid salt. May be included.

  According to the above configuration, fine crystals can be reduced, and the ratio of the compound used for crystal growth can be increased and crystal growth can be performed efficiently. Has an effect that a large crystal can be stably obtained with good reproducibility.

  The method for crystallizing an organic acid according to the present invention is a method for crystallizing an organic acid, which comprises adding an acid to a solution of an organic acid salt and crystallizing the organic acid in order to solve the above problems. Then, after the organic acid starts to crystallize due to the addition of the acid, the base is added to the organic acid crystal-containing solution to convert a part of the organic acid crystal into an organic acid salt and dissolve the acid. May be added. Further, in such a crystallization method, the addition of an acid and the addition of a base are carried out in separate reaction vessels provided in communication with each other while circulating the liquid in the reaction vessels between the reaction vessels, and P is the amount (g) of the organic acid salt in the solution of the organic acid salt before addition, Z is the value obtained by dividing the molecular weight of the organic acid salt by the number of anionic functional groups contained in one molecule of the organic acid salt, and Z is the amount of the base added. The value obtained by dividing (g) by the equivalent (g) of the base is M, the addition time is T (min), the circulation amount of the liquid per unit time is F (ml / min), and the maximum liquid amount in the system is Assuming that the logarithmic average of the minimum liquid volume is L (ml), the value of the expression represented by L × M / (T × F × P × Z) is set to satisfy 0.5 or more and less than 1.5. It is preferred to adjust the amount of the base.

  According to the above configuration, when the degree of supersaturation of the target organic acid is very small, and nucleation is dominant and crystal growth is poor due to immediate precipitation of crystals near the acid dropping, crystals are precipitated with an acid. While dissolving fine crystals derived from new nucleation with a base, reducing the fine crystals and increasing the amount of organic acid salt used for crystal growth, the crystal grain size is stable and reproducible. Can be larger.

In the method for crystallizing an organic acid according to the present invention, the following M / (P × Z) is preferably in a range satisfying the following expression.
Q / (P × Z) −0.3 ≦ M / (P × Z) ≦ Q / (P × Z) −0.03
M: value obtained by dividing the amount (g) of the base added by the equivalent (g) of the base Q: value P obtained by dividing the amount (g) of the acid added before the addition of the base by the equivalent (g) of the acid ： Amount of organic acid salt in solution of organic acid salt before initial acid addition (g)
Z: Value obtained by dividing the molecular weight of the organic acid salt in the solution of the organic acid salt before the initial acid addition by the number of anionic functional groups contained in one molecule of the organic acid salt. According to the above configuration, the crystal growth period becomes longer, High effects can be obtained.

  Further, the amount of the organic acid crystals remaining after the addition of the base is preferably in the range of 1 to 30% by weight of the total crystals precipitated. According to the above configuration, the crystal growth period is lengthened, and a high effect can be obtained.

  Further, a method for producing an organic acid crystal according to the present invention includes, in order to solve the above-mentioned problems, a step of obtaining an organic acid crystal by using the method of crystallizing an organic acid according to the present invention; Isolating the organic acid crystals from the reaction solution containing the crystals.

  According to the above configuration, fine crystals can be reduced, and the ratio of the compound used for crystal growth can be increased and crystal growth can be performed efficiently. However, there is an effect that a large organic acid crystal can be stably obtained with good reproducibility.

  Further, in order to solve the above problems, the crystallization apparatus according to the present invention, a crystallization reaction vessel, an acid supply means for supplying an acid into the crystallization reaction vessel, and a base in the crystallization reaction vessel A base supplying means for supplying the acid, and the acid supplying means and the base supplying means are characterized in that the acid supplying means and the base supplying means include supplying the acid and the base to positions separated from each other in the crystallization reaction vessel.

  According to the above configuration, it is possible to stably obtain a crystal having a large average particle diameter and a large bulk density with good reproducibility.

  Further, the crystallization apparatus according to the present invention includes a first reaction vessel provided with an acid supply means, a second reaction vessel provided with a base supply means, the first reaction vessel and the second reaction vessel. And a liquid circulating means for circulating the reaction liquid between the first reaction vessel and the second reaction vessel.

  According to the above configuration, it is possible to stably obtain a crystal having a large average particle diameter and a large bulk density with good reproducibility.

  According to the present invention, a part of crystals crystallized by reacting a raw material organic acid salt with an acid is converted into an organic acid salt by a base and dissolved, and the organic acid salt-containing liquid is dissolved in the presence of the remaining crystals. By reacting again with an acid underneath, fine crystals can be reduced, and the ratio of the compound used for crystal growth can be increased, and crystal growth can be performed efficiently, so that the average particle diameter is large. The effect is that crystals having a large bulk density can be stably obtained with good reproducibility.

  Further, the crystallizer according to the present invention is suitably used for the crystallization reaction, and by using the crystallizer, a crystal having a large average particle diameter and a large bulk density can be stably obtained with good reproducibility. This has the effect that it can be performed.

An embodiment of the present invention will be described in detail below.
The crystallization method according to the present embodiment is a crystallization method in which an acid is added to a solution of an organic acid salt to precipitate a crystal, and the organic acid crystal is crystallized by reacting the organic acid salt with the acid. In this method, a part is dissolved with a base, and the dissolved organic acid salt is reacted again with an acid in the presence of the remaining organic acid crystals.

  More specifically, the crystallization method according to the present embodiment uses an organic acid salt as a starting compound for crystallization, that is, a starting material at the start of a crystallization reaction (hereinafter, referred to as a starting organic acid salt). This is a method for producing crystals of the desired organic acid by adding an acid to a solution of the raw material organic acid salt, preferably an aqueous solution, and reacting the organic acid salt with the acid. After reacting the raw material organic acid salt to be supplied with an acid to crystallize at least a part of the target organic acid, a part of the organic acid crystal precipitated by the crystallization is converted into an organic acid salt with a base. In this method, an acid is added to the organic acid salt solution and the organic acid salt in the system is reacted again with the acid in a state where the remaining crystals are present.

  The crystallization method according to the present embodiment is roughly divided into the following two methods.

  In the first method, a raw material organic acid salt is reacted with an acid to crystallize a target organic acid, a positive reaction from the raw material to the target substance, and a once-precipitated organic acid crystal are dissolved again with a base. In this method, the reverse reaction from the target substance to the raw material is independently performed. (1) By performing the above-described forward reaction and reverse reaction alternately, the reverse reaction to the above forward reaction is performed. The reaction is carried out with a time difference. The method includes, for example, a method in which the above-described normal reaction and reverse reaction are alternately performed in the same vessel, so that the above-described normal reaction and reverse reaction are performed at different times in the same region. In the above method, the reaction in the next step is performed by transferring the reaction solution after each reaction described above to another container, for example, by performing the reverse reaction by transferring the reaction solution in the reaction to another container after the forward reaction. By performing the reaction, the normal reaction and the reverse reaction may be performed alternately.

  As a preferred example of the first method, at least a part of the organic acid to be precipitated is crystallized by adding an acid to the solution of the raw material organic acid salt, and the base is added to the organic acid crystal-containing liquid to form an organic acid. A method for crystallizing an organic acid comprising converting a part of the acid crystals into an organic acid salt and dissolving the solution, and adding an acid to the solution of the organic acid salt. A crystallization method of adding an acid to precipitate an organic acid crystal, wherein at least a part of all organic acid crystals precipitated when the organic acid salt is completely reacted with the acid, A base is added to the organic acid crystal-containing liquid to convert a part of the organic acid crystals into an organic acid salt and dissolved. Thereafter, an acid is further added to the organic acid salt solution to dissolve the dissolved organic acid. A method of reacting a salt with an acid again in the presence of the remaining organic acid crystals can be mentioned. More specifically, an organic acid salt is used as a starting compound, and an acid is added to a solution of the organic acid salt, preferably an aqueous solution, to react the starting organic acid salt with the acid, so that at least one of the corresponding organic acids is obtained. After crystallizing a portion, a base is added to the crystal of the organic acid precipitated by the crystallization, and a part of the crystal is reacted with the base to be converted into an organic acid salt and dissolved. This is a method in which an acid is added to the salt solution and the organic acid salt is reacted with the acid again in the presence of the remaining crystals to grow the remaining crystals as nuclei (seed crystals).

  That is, in the first method, the acid is added dropwise to the crystallization according to the present embodiment, that is, the raw material organic acid salt to be subjected to neutralization crystallization in the presence of water, and the target organic acid is (I) From an unsaturated state, (II) through a supersaturated state in which crystals do not precipitate beyond the saturation solubility of the organic acid, (III) after the rapid supersaturated state is eliminated by crystal precipitation, (IV) saturated state By adding (V) a base at an arbitrary point in time and returning the amount of acid excluding the amount of neutralization by the base to the point in (II), fine particles which are considered to precipitate at the time of (III) and (IV) above This is a method of dissolving crystals (relatively small crystals among the precipitated crystals), and (VI) dropping an acid again to transfer the dissolved components to crystal growth.

  On the other hand, the second method is a method in which the above-described forward reaction and reverse reaction are performed in parallel and simultaneously. For example, (2) in the same vessel, performing the reverse reaction while performing the forward reaction, Alternatively, (3) the addition of an acid and the addition of a base are performed in separate containers provided in communication with each other while circulating the liquid in the containers between the containers, so that the above-described processes are simultaneously performed in different regions in parallel. This is a method of performing a forward reaction and a reverse reaction. In the above method (2), an acid and a base are supplied by dropping or the like to a position separated from each other, so that a positive reaction area (crystal precipitation area) and a reverse reaction area (partial (Dissolution area), and the above-described normal reaction and reverse reaction are performed in a non-uniform state.

  Specifically, the second method is a method of crystallizing an organic acid by adding an acid to a solution of a raw material organic acid salt and crystallizing the organic acid. After the start, the method includes adding an acid while adding a base to the reaction system to dissolve a part of the organic acid crystal. More specifically, a method in which a base is supplied to an organic acid crystal-containing liquid crystallized by reacting an organic acid salt with an acid and the organic acid salt is reacted with the acid while re-dissolving a part of the crystals. is there.

  That is, the second method is a method of simultaneously adding a base to the organic acid salt while supplying the acid, and mainly dissolves fine crystals derived from new nucleation in the saturated state of (IV) with the base. In this method, the excess is added to crystal growth by dissolving the dissolved component.

  Of the above two methods, the first method is, as shown in (II) above, through a supersaturated state in which crystals do not precipitate even when exceeding the saturation solubility of the target organic acid, and (III) rapid precipitation by crystal precipitation It is suitable when the supersaturation state is eliminated, particularly when the degree of supersaturation is very large and crystals are precipitated at a stroke during dropping.

  Thus, during the dropping of the acid, for example, crystals do not appear due to supersaturation until the beginning of the dropping or immediately before the end of the dropping, and when the crystals are precipitated at a stroke during the dropping, the nucleation is dominant and it is difficult to grow the crystals. The diameter tends to be small.

Therefore, at any time after the precipitation of the crystal, that is, after the rapid supersaturated state of (III) is eliminated, when a base is added at any time in the state of (IV), the crystals precipitated in (IV) , Starting from those having a small particle size. This is because the crystal having a small particle size has a large specific surface area, whereby the fine crystals among the crystals precipitated in (IV) are dissolved, and when the acid is dropped again in (V), the crystals are already dissolved. Since crystals are present in the system, crystal growth is likely to occur with crystals remaining as undissolved nuclei (seed crystals).

  More specifically, when the supersaturation degree of the organic acid is very large and the supersaturation state continues for a long time, for example, the amount (g) of the charged raw material organic acid salt is set to P, and the molecular weight of the charged raw material organic acid salt is changed to P. When the value divided by the number of anionic functional groups in one molecule of the organic acid salt is Z, and the value obtained by dividing the amount (g) of the acid added by the equivalent (g) of the acid is Q ′, Q ′ / (P When the crystal of the organic acid is deposited only when the amount at which × Z) becomes 0.8 is dropped, the primary nucleus in which the crystal has not grown is precipitated at once.

  Therefore, in such a case, the precipitated crystal grows only for the remaining 20%. Therefore, when, for example, 80% of the precipitated crystals are dissolved, the amount of the remaining organic acid salt in the reaction solution increases, while the remaining 20% of the crystals remain, so that the amount of organic acid relative to the precipitated crystals is increased. The ratio of the acid salt becomes much larger than before the crystal dissolution, and the amount of the organic acid salt used for crystal growth becomes much larger. Then, when the amount of the acid corresponding to the remaining organic acid salt is dropped again, the remaining crystals grow as crystals using the crystals as nuclei (seed crystals), so that large crystals can be stably obtained with good reproducibility. Become.

  That is, in the first method, when the degree of supersaturation of the target organic acid is very large and nucleation is dominant and crystal growth is poor due to precipitation of crystals at a stroke during acid dripping, one of the precipitated crystals By dissolving the part, the number of fine crystals is reduced, and the amount of organic acid salt used for crystal growth is increased, so that the crystal grain size is stably increased with good reproducibility.

  Therefore, the first method can be suitably used for crystallization of an organic acid having a relatively high degree of supersaturation, such as nicotinic acid and salicylic acid.

  In the first method, the Q ′ / (P × Z) in the range of (II) is usually in the range of 0.1 to 1.0, preferably in the range of 0.3 to 1.0. It is suitably used for certain compounds.

  On the other hand, when the degree of supersaturation is very small, and crystals are immediately precipitated near the acid drop, new nuclei are generated one after another by the drop of the acid, that is, fine crystals are generated. In such a case, It is preferable to use the second method.

  That is, in the second method, when the degree of supersaturation of the target organic acid is very small and crystals are precipitated immediately near the dropping of the acid, nucleation is dominant and crystal growth is poor. By dissolving fine crystals derived from new nucleation with a base while precipitating, reducing the fine crystals and increasing the amount of organic acid salt used for crystal growth, the crystal grain size is stable and reproducible Can be made larger.

  Even when the above-mentioned second method is adopted, the crystals having a small particle diameter have a large specific surface area. Therefore, the acid is always in excess with respect to the base, that is, the amount of the acid exceeds the amount neutralized by the base. By dropping the acid, only newly generated fine crystals are completely dissolved, and the remaining crystals that are not completely dissolved react with the acid to grow further. Therefore, by repeating this, even when the degree of supersaturation of the target organic acid is very small and crystals are immediately deposited near the acid dropping, the amount of the raw material compound used for crystal growth is reduced while reducing fine crystals. It is possible to increase the grain size of the crystals existing as nuclei.

  Usually, when the range of (II) occupying the dropping time is large, many fine crystals are precipitated in (III), so that the first method has an effect of increasing the particle size more than the second method. large. Conversely, when the range of (II) occupying the dropping time is small, such as when crystals are precipitated immediately after the acid is dropped, the range of (IV) occupying the dropping time becomes large, The second method has a greater effect of increasing the particle size than the first method. However, except for the case where there is no range (IV), the second method always works effectively.

  Therefore, the above-mentioned second method is applicable to neutralization crystallization in general, that is, crystallization of not only compounds having a relatively large degree of supersaturation such as adipic acid but also compounds having a small degree of supersaturation such as biotin. It can be suitably used.

  The above-mentioned second method is suitably used for an organic acid in which Q ′ / (P × Z) is usually 0.4 or less, preferably 0.1 or less in the range of (II).

  The organic acid applicable in the present invention is a compound having a melting point of 50 ° C. or more having a carboxyl group, a sulfonic acid group, a sulfenic acid group, a phosphonic acid group, a phenolic hydroxyl group and the like, and adipic acid, palmitic acid, stearic acid, Aliphatic carboxylic acids such as biotin, aromatic carboxylic acids such as benzoic acid, nicotinic acid, salicylic acid, aromatic sulfonic acids such as benzenesulfonic acid, aromatic sulfenic acids such as phenylsulfenic acid, and aromatics such as phenylphosphonic acid Examples thereof include phenol derivatives such as phosphonic acid, bisphenol A, xylenol, and naphthol. The organic acid salt is a salt soluble in the above-mentioned organic acid solvent, and examples thereof include alkali metal salts such as sodium salt and potassium salt.

  The raw material organic acid salt is subjected to the crystallization reaction as a solution of the raw material organic acid salt. In the solution, the organic acid salt becomes an anion, reacts with an acid to precipitate an organic acid crystal, and reacts with a base to dissolve the crystal.

  When the above-mentioned crystallization is for purification or the like, the organic acid salt may be a solution in which an organic acid is dissolved in a base.

  When the organic acid salt is brought into contact with an acid or a base in the presence of water, it reacts with the acid or the base to crystallize or dissolve.

  In the present embodiment, for example, an organic acid salt solution prepared by dissolving an organic acid salt in water or an alkali, preferably, an organic acid salt aqueous solution is used as a reaction stock solution, and an acid and / or base is added to the reaction stock solution. Although the case of addition will be described by way of example, the present invention is not limited to this, and later, for example, when an acid or base is added to the organic acid salt, the acid or base is added. Water may be added together with the base. Further, even when a raw material organic acid salt solution is prepared in advance, an acid and / or a base may be mixed with water and added.

  Examples of the solvent for dissolving the organic acid salt include an aqueous solvent, specifically, for example, water; an organic solvent mixed with water; or a mixture thereof. The solvent is not particularly limited as long as it is uniformly mixed with water, but is most preferably water.

  Further, as the organic solvent, specifically, for example, methanol, ethanol, isopropanol, acetone, tetrahydrofuran, dioxane, N-methyl-2-pyrrolidone, dimethylsulfoxide, dimethylformamide and the like. It is not limited. These organic solvents may be used alone or in a combination of two or more.

  The base used is not particularly limited as long as the organic acid can be dissolved by adding the base. Examples thereof include sodium hydroxide, potassium hydroxide, ammonia gas, aqueous ammonia, potassium carbonate, sodium carbonate, and sodium bicarbonate. And the like, and preferably, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium bicarbonate. In the present invention, it is preferable that the cation part of the raw material organic acid salt and the cation part of the base used are the same.

  In addition, the acid to be used, in combination with the solvent to be used, may be those having a small solubility of the target compound, that is, those capable of reacting with the raw material compound to crystallize the target compound, Examples include ammonium sulfate, carbon dioxide gas, hydrochloric acid gas, SOx, NOx, and the like. Among these acids, hydrochloric acid and sulfuric acid are preferred because they are easy to handle.

  The crystallization method according to the present embodiment is suitably used, for example, for producing crystals at a neutral pH or lower.

  The crystallization method according to the present embodiment is particularly effective for crystallization of an organic acid that is hardly soluble or insoluble in water as described above, and can be suitably used for producing such an organic acid crystal.

  In the crystallization method according to the present embodiment, once, the organic acid crystals precipitated by the crystallization, at what time, by how much to return to the organic acid salt with a base, the final required acid The amount to be added is determined.

Hereinafter, the first method and the second method will be specifically described with reference to the drawings.
First, the first method will be described.

  Examples of the reaction vessel (crystallization reaction tank) used in the first method include a stirring vessel equipped with a stirrer, which is provided with a disc turbine blade, a paddle blade, a retreating blade such as three retreating blades, an anchor blade, and the like. However, the reaction vessel is not particularly limited as long as it can be used for the reaction between an organic acid salt as a raw material and an acid or a base, and its scale (capacity), shape, material and the like are not limited. Is not particularly limited.

  As the reaction vessel, a reaction vessel having a jacket on the outer wall side of the reaction vessel, for example, capable of cooling or heating the reaction solution in the reaction vessel through the reaction vessel by passage of a cooling medium or a heating medium is preferably used. Can be The reaction vessel having such a jacket facilitates control of the reaction temperature such as removal of heat of neutralization.

The rotation speed of the stirring by the stirrer (stirring blade) is preferably set such that the stirring power per unit volume in the reaction vessel is in the range of 0.05 to 2.0 kW / m ³ , More preferably, it is set to be within the range of 0.4 kW / m ³ .

  Further, the reaction vessel may have a baffle such as a plate baffle, a beaver tail baffle, a finger baffle, a disk type baffle, a donut type baffle, etc., in addition to the stirring blade.

FIG. 1 shows an example of a crystallization apparatus suitably used in the first method.
A crystallization apparatus 1 shown in FIG. 1 includes a reaction vessel 2 as a crystallization reaction tank used for a crystallization reaction, an acid supply line 3 (acid supply means) for supplying an acid into the reaction vessel 2, A base supply line 4 (base supply means) for supplying a base into the container 2 is provided.

  The reaction vessel 2 is provided with a stirrer 5 for stirring and reacting the unreacted reaction solution introduced into the reaction vessel 2. In addition, the reaction vessel 2 is provided with a jacket 6 having a not-shown conduction port serving as an inlet or an outlet for a heat medium such as hot water on the outer wall side.

  The acid supply line 3 includes an acid storage tank 7 for storing an acid, hollow connecting pipes 8 and 9 serving as acid supply paths (flow paths), and a dropping pipe 10 for dropping and supplying acid into the reaction vessel 2. And an acid supply pump 11 provided between the connection pipes 8 and 9 to send out the acid stored in the acid storage tank 7 to the drip pipe 10 via the connection pipes 8 and 9. It has.

  The base supply line 4 includes a base storage tank 12 for storing a base, hollow connecting pipes 13 and 14 serving as base supply paths (flow paths), and a drop for supplying a base dropwise into the reaction vessel 2. The base 15 is provided between the pipe 15 and the connecting pipes 13 and 14, and sends out the base stored in the base storage tank 12 to the dropping pipe 15 through the connecting pipes 13 and 14. A pump 16 is provided.

Next, an example of a crystallization operation using the crystallization apparatus 1 will be described below.
First, a raw material organic acid salt solution is prepared by dissolving the raw material organic acid salt in water or an alkali. Next, the raw material organic acid salt solution is introduced into the reaction vessel 2 as a reaction stock solution. Next, the acid stored in the acid storage tank 7 is supplied to the reaction liquid in the reaction vessel 2 from the dropping pipe 10 through the connecting pipes 8 and 9 using the pump 11. The acid is, for example, diluted in water so as to have a desired concentration and stored in the acid storage tank 7 in advance. In the present embodiment, for example, a 6N hydrochloric acid aqueous solution is used, but the present invention is not limited to this.

  As described above, the organic acid salt in the undiluted reaction solution reacts with the acid introduced into the reaction vessel 2, whereby the organic acid becomes supersaturated in (II) and rapidly in (III). After elimination of the supersaturated state, the state of (IV) is reached and crystals are precipitated.

  Next, at any time in the above (IV), the base stored in the base storage tank 12 is supplied to the reaction solution in the reaction vessel 2 from the dropping pipe 15 through the connecting pipes 13 and 14 using the pump 16. Thus, the fine crystals in the reaction vessel 2, that is, a part of the precipitated crystals are dissolved.

  The supply timing of the base may be after once crystallizing all of the target organic acid from the raw material organic acid salt, or even after once crystallizing a part of the target organic acid from the raw material organic acid salt. In order to minimize the amount of the base and the acid used, it is preferable to supply the latter, particularly, the base to the reaction solution at the time when the crystals are precipitated.

  Precipitation of crystals can be confirmed visually, or a change in pH can be detected using a pH meter by utilizing the fact that the pH greatly fluctuates at the moment the crystals come out. Of course, without confirming the precipitation of crystals, assuming that the number of anionic functional groups in the charged organic acid salt is 1, the addition amount of the acid is divided by the equivalent of the acid, and the excess amount is 1 or more. May be used to control the system so that a series of reactions are all performed automatically by precipitating crystals.

  Next, the acid stored in the acid storage tank 7 is again supplied to the reaction liquid in the reaction vessel 2 from the dropping pipe 10 through the connecting pipes 8 and 9 using the pump 11. Thereby, the organic acid salt of the crystals dissolved by the base is again subjected to crystallization, and crystals having a large average particle diameter can be obtained by crystal growth.

  In the crystallization method according to the present embodiment, the supplied amount is more than the value obtained by dividing the added amount (g) of the supplied acid by the equivalent amount (g) of the acid (hereinafter, referred to as an acid equivalent value). The value obtained by dividing the amount (g) of the base to be added by the equivalent (g) of the base (hereinafter sometimes referred to as base equivalent) is small, and the anionic functional group contained in the organic acid salt is reduced. The amount of acid neutralized by the base in addition to the amount of acid needed to acidify all is used for the charged organic acid salt. In other words, in the crystallization method according to the present embodiment, the value obtained by dividing the amount (g) of the charged organic acid salt by the equivalent (g) of the organic acid salt from the supplied acid equivalent value and the supplied base equivalent The amounts of acids and bases used are determined so that the sum of the values is small. The amount of the base used may be set so that the amount of the acid excluding the amount neutralized by the base is reduced to the range of the above (II), and once the acid is added and crystallized, The value obtained by dividing the amount of the organic acid crystals remaining dissolved even when the base was supplied by the equivalent of the organic acid is Q, the amount (g) of the raw material organic acid salt is P, and the molecular weight of the raw material organic acid salt is the organic acid. When the value divided by the number of anionic functional groups in one molecule of the salt is Z, Q / (P × Z) is usually in the range of 0.01 to 0.3, preferably 0.05 to 0.2. The amount of the base used may be set so as to fall within the range described above. Thereby, the crystal growth period is lengthened, and a high effect can be obtained.

  For example, when the organic acid is adipic acid, the amount of crystals remaining dissolved even when the base is supplied is usually 1 to 1 of all crystals precipitated when the raw material organic acid salt is completely reacted with the acid. The above base may be added within a range of 30% by weight (in other words, within a range of 1 to 30% by weight of the charged organic acid salt), preferably within a range of 5 to 20% by weight.

  More specifically, in the above reaction, the value obtained by dividing the acid equivalent value added first by (P × Z) is usually in the range of 0.33 to 3, preferably 0.5 to 1. 3 is within the range. Further, the value obtained by dividing the base equivalent value to be used by the above (P × Z) is usually 0.03 to 0.3 subtracted from the value obtained by dividing the acid equivalent value to be added first by the above (P × Z). It is within the range of values, and preferably within the range of 0.05 to 0.15 subtracted from the value obtained by dividing the initially added acid equivalent value by the above (P × Z). As for the value obtained by dividing the acid equivalent value used after the base addition by the above (P × Z), the value obtained by dividing the acid equivalent value used first by the above (P × Z) and the acid equivalent value used after the base addition are used. The value obtained by subtracting the value obtained by dividing the used base equivalent value by the above (P × Z) from the sum with the value obtained by the above (P × Z) is usually in the range of 0.9 to 3, preferably from 0.9 to 3. It is in the range of 1 to 1.3.

  The supply time, supply position, and supply method of the acid and the base are not particularly limited, and the supply of the acid and the base is not necessarily performed by using the acid supply line 3 or the base supply line 4 having the above-described configuration. It is not necessary to use, and of course, the supply of the acid and the base does not necessarily require the dropping tubes 10 and 15. When the dropping tubes 10 and 15 are used, each of the dropping tubes 10 and 15 can be provided at an arbitrary position in the reaction vessel 2.

  The material, size, and the like of each member constituting the crystallizer 1 are not particularly limited as long as they can be used for the reaction between the above-mentioned raw material organic acid salt and an acid or a base.

  Further, the amount of the undiluted reaction solution to be charged into the reaction vessel 2 may be appropriately set according to the concentration of the component to be crystallized, the amounts of the acid and base used, and is not particularly limited.

  In addition, conditions such as the reaction time, reaction temperature, and reaction pressure in each of the above-mentioned reactions may be appropriately set according to the type and amount of the raw material organic acid salt, the combination with the acid or base, and the like, and are particularly limited. is not.

  During the crystallization, by adding an acid and a base to the above-mentioned undiluted reaction solution, the amount of the reaction solution slightly increases, but the reaction vessel 2 and the reaction conditions in consideration of the increase in the amount of the solution are changed. It is desirable to use.

Next, the second method will be described.
As the second method, when the reverse reaction is performed while performing the normal reaction in the same reaction vessel as described above, the crystallization apparatus 1 shown in FIG. 1 is used as the crystallization apparatus used in the method. Can be.

  Examples of the reaction vessel 2 (crystallization reaction tank) used in the second method include a disk turbine blade, a paddle blade, a retreating blade such as three retreating blades, a stirring tank equipped with a stirrer, and the like. The same reaction vessel as the reaction vessel 2 used in the first method can be used. The reaction vessel 2 is not particularly limited as long as it can be used for the reaction between an organic acid salt and an acid or a base, and its scale (capacity), shape, material, and the like are not particularly limited.

  Also in the second method, the reaction vessel 2 is provided on the outer wall side of the reaction vessel, for example, with a jacket capable of cooling or heating the reaction liquid in the reaction vessel through the reaction vessel through conduction of a refrigerant or a heat medium. Is preferably used. Since the reaction vessel 2 has such a jacket, control of the reaction temperature such as removal of heat of neutralization becomes easy.

The rotation speed of the stirring by the stirrer 5 (stirring blade) is preferably set such that the stirring power per unit volume in the reaction vessel 2 is in the range of 0.05 to 2.0 kW / m ³ . More preferably, it is set to be in the range of from 0.5 to 0.3 kW / m ³ .

  Further, the reaction vessel 2 may have a baffle such as a plate baffle, a beaver tail baffle, a finger baffle, a disk-type baffle, a donut-type baffle other than the stirring blade. In particular, as the second method, when the reverse reaction is performed while performing the normal reaction in the same reaction vessel 2 as shown in the above (2), the inside of the reaction vessel 2 is partially By partitioning into acid and acid, the acid and the base can be prevented from being wastefully consumed by neutralization.

  In this case as well, each of the dropping tubes 10 and 15 can be provided at an arbitrary position of the reaction vessel 2 shown in FIG. 1. In the case of addition, the acid and the base are hardly mixed with each other from the flow pattern in the reaction vessel 2 to be used in order to suppress the acid and the base from being wasted by the neutralization. It is desirable that the acid and the base are supplied at a position where the acid and the base are hardly in contact with each other, and it is desirable that the two drop tubes 10 and 15 are provided as far apart from each other as possible.

  In the crystallization apparatus 1 shown in FIG. 1, a dropping tube 10 for supplying an acid is provided at the bottom of the reaction vessel 2, while a dropping pipe 15 for supplying a base is provided for the reaction solution in the reaction vessel 2. It is provided above the liquid surface, that is, at the top in the reaction vessel 2, whereby the acid is supplied to the bottom in the reaction vessel 2 and the base is supplied to the top in the reaction vessel 2. However, the present invention is not limited to this as long as the two dropping tubes 10 and 15 are formed at positions separated from each other as described above.

  However, since the fine crystals tend to move upward by stirring, the acid is removed from the vicinity of the stirrer 5 (stirring blade) in the reaction vessel 2 using the dropping tubes 10 and 15 as shown in FIG. Preferably, the base is supplied to the surface of the reaction solution which is a stirring liquid. That is, in the crystallization apparatus 1, the dropping tube 10 for supplying acid is provided at the bottom of the reaction vessel 2, and the dropping pipe 15 for supplying base is provided at the top of the reaction vessel 2. This is desirable for producing crystals having a large average particle diameter by reducing fine crystals.

Next, an example of the crystallization operation using the crystallization apparatus 1 in the second method will be described below.
First, a raw material organic acid salt solution is prepared by dissolving the raw material organic acid salt in water or an alkali. Next, the raw organic salt solution is introduced into the reaction vessel 2 as a reaction stock solution. Up to this point, the method is the same as the above-mentioned first method. However, when the above-mentioned method (2) is used, the acid stored in the acid storage tank 7 using the pump 11 is dropped through the connecting pipes 8 and 9 to the dropping pipe 10. The base stored in the base storage tank 12 is supplied to the reaction solution in the reaction vessel 2 from the dropping pipe 15 through the connecting pipes 13 and 14 while being supplied to the reaction solution in the reaction vessel 2 from the pump 16. Supply.

  In this case, in order to efficiently perform the above-described forward reaction and reverse reaction, it is desirable to start the supply of the base after the start of the supply of the acid and after the crystals start to precipitate.

  In the reaction solution, a forward reaction predominates near the acid supply position, and a reverse reaction predominantly occurs near the base supply position. Crystals precipitated near the supply position of the acid dissolve fine crystals near the supply position of the base by stirring, and the remaining crystals grow near the dropping position of the acid. In the above method, this reaction is repeated in the reaction vessel 2, and the remaining crystals gradually become larger.

  In the above-mentioned crystallization method, the acid and the base so that the sum of the value obtained by dividing the amount of the raw material organic acid salt by the equivalent of the organic acid salt and the supplied base equivalent value becomes smaller than the supplied acid equivalent value. Is determined.

  The value obtained by dividing the used base equivalent value by the above (P × Z) is usually in the range of 0.5 to 10, and preferably in the range of 0.8 to 2.5.

  The value obtained by dividing the used acid equivalent value by the above (P × Z) is usually 0.9 to 1.5, preferably 1 to the value obtained by dividing the used base equivalent value by the above (P × Z). 0.0 to 1.3.

  The supply of the base may be performed at a constant rate, but it is more preferable to drop the mixture intermittently because the non-uniformity in the reaction vessel 2 increases and the average particle diameter of the crystals tends to increase.

  In the above-mentioned crystallization method, it is preferable that the base equivalent value relative to the supplied acid equivalent value is relatively large because the average particle size of the crystals tends to be large. Further, it is preferable that the base concentration is higher, since it tends to increase the average particle diameter of the crystals.

  The amount of the base used, the dropping time, and the like vary depending on the flow pattern of the crystallizer 1, that is, the mixing state caused by the flow pattern of the reaction vessel 2 in this case. It is desirable to be done. That is, in the above method, it is desirable to optimize the balance of the stirring conditions, the dropping position, the dropping speed, and the dropping amount so that the reaction vessel 2 has an appropriate stagnation.

  Also, instead of directly adding the base into the crystallization reaction vessel as described above, the reaction solution is transferred to a reaction vessel different from the crystallization reaction vessel, the base is added, and the base is returned to the crystallization reaction vessel again. A series of reactions described above may be performed.

  Hereinafter, as a method for performing the above-described series of reactions by transferring the reaction solution into a reaction vessel different from the crystallization reaction vessel, adding a base, and returning the reaction solution to the crystallization reaction vessel again, as described in (3) above. Referring to FIG. 2, a method in which a forward reaction and a reverse reaction are performed in different reaction vessels, and the solution in the vessel is circulated between the different reaction vessels and the above-described forward reaction and reverse reaction are alternately repeated. This will be specifically described.

FIG. 2 shows an example of a crystallization apparatus suitably used in the above method.
A crystallization apparatus 20 shown in FIG. 2 includes a first reaction vessel 21 as a crystallization reaction vessel for crystallizing a raw material organic acid salt with an acid, and a crystal deposited by crystallization in the first reaction vessel 21. A second reaction vessel 31 as a reaction vessel for reverse reaction for dissolving a part of the base with a base, an acid supply line 40 (acid supply means) for supplying an acid into the first reaction vessel 21, A base supply line 50 (base supply line) for supplying a base into the second reaction vessel 31, and a reaction solution circulation line for circulating a reaction solution between the first reaction vessel 21 and the second reaction vessel 31 60 (reaction liquid circulation means).

  The first reaction container 21 is provided with a stirrer 22 that stirs and reacts the unreacted reaction solution introduced into the first reaction container 21. Further, the first reaction vessel 21 is provided on its outer wall side with a jacket 23 having a conduction port (not shown) serving as an inlet or an outlet for a heat medium such as hot water.

  Similarly, the second reaction vessel 31 is provided with a stirrer 32 for stirring and reacting the reaction solution introduced into the second reaction vessel 31. Further, the second reaction vessel 31 is provided on its outer wall side with a jacket 33 having a conduction port (not shown) serving as an inlet or an outlet of a heat medium such as hot water.

  The acid supply line 40 includes an acid storage tank 41 for storing an acid, hollow connecting pipes 42 and 43 serving as acid supply paths (flow paths), and an acid supply line for supplying the acid dropwise into the first reaction vessel 21. An acid supply, which is provided between the dropping pipe 44 and the connecting pipes 42 and 43 and sends out the acid stored in the acid storage tank 41 to the dropping pipe 44 via the connecting pipes 42 and 43. Pump 45 is provided.

  The base supply line 50 supplies a base storage tank 51 for storing a base, hollow connecting pipes 52 and 53 serving as base supply paths (flow paths), and a base to be dropped into the second reaction vessel 31. Pipe for supplying the acid stored in the acid storage tank 51 to the dropping pipe 54 via the connecting pipes 52 and 53, and a base provided between the connecting pipes 52 and 53. A supply pump 55 is provided.

  In addition, each configuration of the first and second reaction vessels 21 and 31, the acid supply line 40, the base supply line 50, and the like, and each reaction stirring rotation speed in the first and second reaction vessels 21 and 31 The crystallization conditions such as above are as described above, and can be set in the same manner as in the case where the crystallization apparatus 1 is used. That is, the crystallization conditions in the crystallization apparatus 20 are such that the forward reaction and the reverse reaction are performed using separate reaction vessels, respectively, and the first reaction vessel 21 and the second reaction vessel The crystallization conditions can be set in the same manner as the crystallization conditions according to the second method using the crystallization apparatus 1 described above, except that the reaction solution is circulated to and from the reaction vessel 31.

  The reaction liquid circulation line 60 connects the first reaction container 21 and the second reaction container 31 and sends a reaction liquid in the first reaction container 21 to the second reaction container 31. And a return path for connecting the first reaction vessel 21 and the second reaction vessel 31 and sending out the reaction solution in the second reaction vessel 31 to the first reaction vessel 21. .

  A suction pipe 61 for sucking the reaction liquid in the first reaction vessel 21, hollow connection pipes 62 and 63 serving as flow paths for the reaction liquid, A pump 64 for circulating the reaction solution, which is provided between the tubes 62 and 63 and sends the reaction solution in the first reaction container 21 to the second reaction container 31 through the connection tubes 62 and 63, Is provided.

  Further, on the return path of the reaction liquid circulation line 60, a suction pipe 67 for sucking the reaction liquid in the second reaction vessel 31, a hollow connection pipe 68/69 serving as a flow path of the reaction liquid, A pump for circulating the reaction solution, which is provided between the connection pipes 68 and 69 and sends the reaction solution in the second reaction vessel 31 to the first reaction vessel 21 via the connection pipes 68 and 69. 70 are provided.

  Thereby, the reaction liquid in each of the crystallizers 21 and 31 is drawn out by each suction pipe 61 and 67 through each connecting pipe 62 and 68 to each pump 64 and 70, and further, each of the connecting pipes 63 and 69. Is introduced into each of the reaction vessels 21 and 31 so as to be circulated between the respective reaction vessels 21 and 31.

  The reaction vessels 21 and 31 include, for example, a stirring and mixing tank, a line mixer, and a static mixer, but are not particularly limited. As the reaction vessels 21 and 31, the same reaction vessels as the above-described reaction vessel 2 can be used, and there is no particular limitation as long as they can be used for the reaction between the raw material organic acid salt and the acid and base. However, its scale (capacity), shape, material, and the like are not particularly limited.

Next, an example of a crystallization operation using the crystallization device 20 will be described below.
First, a raw material organic acid salt solution is prepared by dissolving the raw material organic acid salt in water or an alkali. Next, the raw material organic acid salt solution is introduced into the first reaction vessel 21 as a reaction stock solution. Next, the acid stored in the acid storage tank 41 is supplied to the reaction liquid in the reaction vessel 21 from the dropping pipe 44 through the connecting pipes 42 and 43 using the pump 45. As described above, the acid is, for example, diluted in water so as to have a desired concentration and stored in the acid storage tank 41 in advance.

  The raw material organic acid salt in the first reaction vessel 21 reacts with the acid introduced into the first reaction vessel 21 and precipitates as crystals. The reaction liquid in which the precipitated crystals are dispersed is drawn out of the first reaction vessel 21 by using a suction pipe 61 by a pump 64 provided in a feed line of a reaction liquid circulation line 60, and is connected to a connection pipe 62. It is introduced into the second reaction vessel 31 through 63.

  In the second reaction vessel 31, the base stored in the base storage tank 51 is supplied dropwise from the dropping pipe 54 by the pump 55 through the connecting pipes 52 and 53. For this reason, the crystals in the reaction solution introduced into the second reaction vessel 31 react with the base supplied into the second reaction vessel 31 and a part thereof dissolves, and the reaction solution contains Only relatively large crystals remain. As described above, for example, the base is diluted with water so as to have a desired concentration and stored in the base storage tank 51 in advance.

  The reaction liquid in which the fine crystals are dissolved in the second reaction vessel 31 is removed from the second reaction vessel 31 by using a suction pipe 67 by a pump 70 provided on the return path of the reaction liquid circulation line 60. It is withdrawn and returned into the first reaction vessel 21 through the connecting pipes 68 and 69.

  In the first reaction vessel 21, new crystals are generated by the acid dropped from the acid storage tank 41 through the dropping pipe 44, while the reaction liquid circulated through the second reaction vessel 31 is formed. The crystal grows with the crystal as a nucleus (seed crystal).

  The reaction liquid in the first reaction vessel 21 is again introduced into the second reaction vessel 31 through the feed line of the reaction liquid circulation line 60, and the fine liquid newly generated in the first reaction vessel 21 here. These crystals are dissolved and returned to the first reaction vessel 21 again. By repeating this, a crystal having a larger average particle diameter is produced.

  When the crystallizer 20 is used, the base is supplied to the second reaction vessel 31, and the reaction liquid supplied to the second reaction vessel 31 by the feed line of the reaction liquid circulation line 60. By dissolving the fine crystals therein, in the return path of the reaction liquid circulation line 60, relatively large crystals are returned to the first reaction vessel 21 through the return path of the reaction liquid circulation line 60. Can be observed.

  With the use of the above-mentioned crystallization apparatus 20, the circulation of the reaction solution can be controlled by the pumps 64 and 70, the amount of the circulation, the timing of sending the reaction solution and the like. Therefore, by using the crystallizer 20 described above, for example, the reaction time in each of the above-described reaction vessels, that is, the first reaction vessel 21 and the second reaction vessel 31 can be adjusted. Needless to say, the crystallization can be performed in a state where the reaction solution is constantly circulated using the crystallization device 20.

  The crystallization conditions when using the above-described crystallization device 20 are set in the same manner as the crystallization conditions in the second method using the crystallization device 1.

For example, the rotation speed of the stirring by the stirrer 22 (stirring blade) is set so that the stirring power per unit volume in the first reaction vessel 21 is in the range of 0.05 to 2.0 kW / m ^3. It is more preferably set to be in the range of 0.05 to 0.3 kW / m ³ .

However, when the above-mentioned crystallizer 20 is used, the stirring rotation speed on the base supply side may be sufficient to dissolve the crystals. For example, the stirring rotation speed by each of the stirrers 32 (stirring blades) may be used. The number is preferably set so that the stirring power per unit volume in the second reaction vessel 31 is in the range of 0.1 to 2.0 kW / m ³ .

  That is, in the stirrer 22, it is desirable to stir relatively slowly so as not to break the crystal. However, in the stirrer 32, it is not particularly limited, and it is preferable to stir relatively strongly because the dissolution of the crystal can be performed quickly. .

  Also in the above-mentioned crystallization method, the acid is adjusted so that the sum of the value obtained by dividing the amount of the raw material organic acid salt by the equivalent of the organic acid salt and the supplied base equivalent value is smaller than the supplied acid equivalent value. And the amount of base used is determined.

  The value obtained by dividing the used base equivalent value by the above (P × Z) is usually in the range of 0.1 to 2.5, and preferably in the range of 0.75 to 1.5.

  The value obtained by dividing the used acid equivalent value by the above (P × Z) is usually 0.9 to 1.5, preferably the value obtained by dividing the used base equivalent value by the above (P × Z). Is within a range obtained by adding 1.0 to 1.2.

  However, in the above method, it is better that the amount of the base used is longer when the reaction vessel 31 is alkaline, and the amount (g) of the charged raw material organic acid salt is P, and the molecular weight of the charged raw material organic acid salt is the same as the organic acid. The value divided by the number of anionic functional groups in one molecule of the acid salt is Z, the base equivalent value (the value obtained by dividing the amount of base added (g) by the equivalent of the base (g)) is M, and the dropping time is T (min). ), The circulation amount of the reaction solution per unit time is F (ml / min), and the logarithmic average of the maximum solution amount and the minimum solution amount in the system, that is, the crystallizer 20 (that is, the first reaction vessel 21 and Assuming that the liquid amount in the second reaction vessel 31 and the logarithmic average of the maximum amount and the minimum amount of the total amount of the liquid amounts in the connection pipes 62, 63, 68, and 69) are L (ml), then (L × M) / It is preferable that the value (α) represented by (T × F × P × Z) is 0.5 or more and less than 1.5. Specifically, it is desirable to set the value to be in a range of 0.7 or more and less than 1.1.

  In the crystallization apparatus 20 shown in FIG. 2, the reaction liquid is extracted from the first reaction vessel 21 and the second reaction vessel 31 by using the suction pipes 61 and 67, but the present invention is not limited to this. Instead, for example, a reaction liquid outlet may be provided at the bottom or the peripheral wall of the first reaction container 21 or the second reaction container 31, and the reaction liquid may be extracted from the reaction liquid outlet. That is, the connection pipes 62, 63, 68, 69 and the suction pipes 61, 67 constituting the reaction liquid circulation line 60 are also connected to arbitrary parts of the reaction vessels 21, 31 similarly to the dropping pipes 44, 54. can do.

  Further, in the crystallizer 20 shown in FIG. 2, the reaction solution discharged from the first reaction container 21 is supplied to the upper part of the second reaction container 31 by the passage of the reaction solution circulation line 60, and the reaction solution circulation is performed. Although the reaction solution discharged from the second reaction vessel 31 is supplied to the upper part of the first reaction vessel 21 by the return path of the line 60, the configuration of the crystallization apparatus 20 is not limited to this. Not something. In addition, a plurality of reaction vessels, supply lines, circulation lines, and the like may be provided.

  Also in the second method, the conditions such as the amount of the reaction solution to be initially charged into the first reaction vessel 31, the reaction time, the reaction temperature, and the reaction pressure in each reaction are determined by the type of the raw material organic acid salt. The amount may be set as appropriate according to the combination of the compound with an acid or a base, and the like, and is not particularly limited.

  The organic acid crystal liquid thus obtained can be isolated by ordinary filtration. As the filtration method, any filtration method such as, for example, centrifugal filtration, pressure filtration, vacuum filtration, gravity flow filtration and the like may be employed.

  As described above, according to the present embodiment, fine crystals can be reduced by crystallization by each of the crystallization methods described above, and the ratio of the organic acid used for crystal growth can be increased to improve the efficiency. Since the crystal can be grown well, a crystal having a large average particle diameter and a powder having a large bulk density can be stably obtained with good reproducibility.

  It is expected that the crystals obtained by using each of the above-mentioned crystallization methods have an average particle size shifted to a large particle side. Thereby, when the reaction liquid containing the crystals is separated by filtration, the effect that the filterability of the reaction liquid is improved, and the obtained target organic acid powder has a large bulk density and a high fluidity The effect that it becomes better can be obtained.

  The present invention is not limited to the embodiments described above, and various modifications can be made within the scope shown in the claims. That is, embodiments obtained by combining technical means appropriately changed within the scope of the claims are also included in the technical scope of the present invention.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

[Example 1]
12.02 g of salicylic acid, 15.17 g of 8 mol / l (20 ° C.) aqueous sodium hydroxide solution, and 499.87 g of water were placed in a 1000 ml separable flask (reaction vessel) equipped with three retreating blades (stirring machine) having a radius of 30 mm. In addition, salicylic acid was completely dissolved to obtain a solution (raw solution) of the raw material organic acid salt.

  Subsequently, the stirring rotation speed of the three retreating blades was set to 370 rpm, and 19.14 g of 6 mol / l (20 ° C.) hydrochloric acid was applied to the surface of the separable flask at 30 ° C. using a metering pump. Was added dropwise over 29 minutes. Seven minutes after the start of the dropping of hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, after charging 11.02 g of an 8 mol / l sodium hydroxide aqueous solution (20 ° C.) over 8 minutes to the surface of the liquid in the separable flask, the metering pump was used to charge the surface of the liquid in the separable flask. 12.75 g of 6 mol / l (20 ° C.) hydrochloric acid was added dropwise over 20 minutes.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain 10.35 g of salicylic acid crystals. Next, the volume-based average diameter of the crystals was measured with a laser diffraction particle size distribution analyzer (“Master Sizer S Long bed” (trade name) manufactured by Malvarn Instruments Ltd., UK). It was 8 μm.

[Comparative Example 1]
In a 1000 ml separable flask (reaction vessel) equipped with three retreating blades (stirrer) having a radius of 30 mm, 12.02 g of salicylic acid, 15.18 g of an aqueous 8 mol / l (20 ° C.) sodium hydroxide solution, and 500.01 g of water were placed. In addition, salicylic acid was completely dissolved to obtain a solution (raw solution) of the raw material organic acid salt.

  Then, the stirring rotation speed of the three retreating blades was set to 370 rpm, and 19.15 g of 6 mol / l (20 ° C.) hydrochloric acid was applied to the liquid surface of the separable flask at an internal temperature of 30 ° C. using a quantitative pump. Was added dropwise over 30 minutes. Ten minutes after the start of the dropwise addition of hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain 9.97 g of salicylic acid crystals. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 1, the volume-based average diameter was 53.3 μm.

[Example 2]
14.62 g of adipic acid, 17.53 g of an aqueous 8 mol / l (20 ° C.) sodium hydroxide solution, and 19.9.0 g of water were placed in a 500 ml separable flask (reaction vessel) equipped with three retreating blades (stirring machine) having a radius of 23 mm. Was added to completely dissolve adipic acid to obtain a solution (raw solution) of the raw material organic acid salt.

  Subsequently, the stirring rotation speed of the three retreating blades was set to 171 rpm, and 40.26 g of 6 mol / l (20 ° C.) hydrochloric acid was added to the above separator using an addition funnel (dropping tube) at an internal temperature of 30 ° C. The solution was dropped into the lower portion of the bull flask over 40 minutes.

  Sixteen minutes after the start of the dropping of hydrochloric acid, 15.95 g of an 8 mol / l (20 ° C.) aqueous sodium hydroxide solution was dropped on the surface of the reaction solution in the separable flask using a dropping funnel. At the same time, the dropwise addition was completed in 24 minutes.

  Thereafter, the dropping funnel for dropping hydrochloric acid and the dropping funnel for dropping sodium hydroxide used in the above reaction were washed with 3.19 g and 2.08 g of water, respectively.

Subsequently, the reaction liquid in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain adipic acid crystals. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 1, the volume-based average diameter was 175 μm. When 1.50 g of the obtained crystals of adipic acid were charged into a glass tube having an inner diameter of 8 mm, the height of the powder was 90 mm, and the bulk density of the powder was 332 kg / m ³ .

[Comparative Example 2]
14.62 g of adipic acid, 17.53 g of an aqueous solution of 8 mol / l (20 ° C.) sodium hydroxide and 199.04 g of water were added to a 500 ml separable flask equipped with three retreating blades having a radius of 23 mm, and adipic acid was completely added. To give a solution of the raw material organic acid salt (reaction stock solution).

  Subsequently, the stirring rotation speed of the three retreating blades was set to 316 rpm, and 21.96 g of 6 mol / l (20 ° C.) hydrochloric acid was placed in the separable flask at an internal temperature of 30 ° C. using a dropping funnel. The reaction solution was dropped on the liquid surface over 26 minutes, and the dropping funnel was washed with 4.12 g of water.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain adipic acid. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 1, the volume-based average diameter was 129 μm.

When 1.50 g of the obtained crystals of adipic acid were charged into a glass tube having an inner diameter of 8 mm, the height of the powder was 112 mm, and the bulk density of the powder was 267 kg / m ³ .

[Example 3]
50.13 g of biotin, 35.88 g of an 8 mol / l (20 ° C.) aqueous sodium hydroxide solution, and water 600 were placed in a 1000 ml separable flask (first reaction vessel) equipped with three retreating blades (stirrer) having a radius of 30 mm. Then, biotin was completely dissolved to obtain a solution of the raw organic acid salt (reaction stock solution), and the stirring rotation speed of the three retreating blades was set at 300 rpm. Also, 100.22 g of water was added to a 500 ml separable flask (second reaction vessel) equipped with three retreating blades (radius: 23 mm) having a radius of 23 mm, and the stirring rotation speed of the three retreating blades was set to 350 rpm. . A dip tube is installed in the first reaction vessel, and the content (reaction liquid) in the first reaction vessel is pumped at 32.8 ml / min using a pump. The liquid was sent to the liquid surface. At the same time, a dip tube is set in the second reaction vessel, and the contents (reaction liquid) in the second reaction vessel are pumped at 32.8 ml / min using a pump. The solution was sent to the liquid surface of the product, and the contents in both reaction vessels were circulated for 10 minutes.

  Subsequently, 101.25 g of 6 mol / l (20 ° C.) hydrochloric acid was applied to the liquid surface in the first reaction vessel for 45 minutes by using a metering pump at an internal temperature of 30 ° C. while circulating at the above flow rate. The solution was dropped. At the same time, 48.96 g of an 8 mol / l (20 ° C.) aqueous sodium hydroxide solution was supplied to the contents of the second reaction vessel by using a metering pump at an internal temperature of 30 ° C. while circulating at the above flow rate. The solution was dropped on the surface over 45 minutes.

After the completion of the dropwise addition, the contents in both reaction vessels were circulated at the above flow rate for 10 minutes. Subsequently, the reaction solutions in both reaction vessels were filtered under reduced pressure and dried under reduced pressure to obtain 49.83 g of biotin crystals. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 1, the volume-based average diameter was 24.1 μm. In addition, the UtoTakashi density and Mitsukasa density of the crystal was measured in the powder properties measuring device (Hosokawa Micron of "Powder Tester" (trade name)), met each ^{219kg / m 3, 402kg / m} 3 Was.

[Comparative Example 3]
50.02 g of biotin, 35.87 g of 8 mol / l (20 ° C.) aqueous sodium hydroxide solution, and 700.1 g of water were placed in a 1000 ml separable flask (reaction vessel) equipped with three retreating blades (stirrer) having a radius of 30 mm. In addition, biotin was completely dissolved to obtain a solution of the raw organic acid salt (reaction stock solution), and the stirring rotation speed of the three retreating blades was set to 300 rpm. Subsequently, 44.93 g of 6 mol / l (20 ° C.) hydrochloric acid was added dropwise to the liquid surface of the contents (reaction liquid) in the separable flask over 40 minutes by using a metering pump at an internal temperature of 30 ° C. .

Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain 49.96 g of biotin crystals. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 3, the volume-based average diameter was 14.6 μm. Further, the UtoTakashi density and Mitsukasa density of the crystal was measured in the same powder properties measuring instrument as in Example 3 were respectively ^{188kg / m 3, 348kg / m} 3.

[Example 4]
In a 500 ml separable flask (reaction vessel) equipped with three retreating blades (stirrer) having a radius of 23 mm, 20.13 g of nicotinic acid, 28.50 g of an 8 mol / l (20 ° C.) aqueous sodium hydroxide solution, and 300.73 g of water Was added to completely dissolve nicotinic acid to obtain a solution (raw solution) of the raw material organic acid salt. Subsequently, the stirring rotation speed of the three retreating blades was set to 300 rpm, and 6 mol / l (at the internal temperature of 5 ° C.) was applied to the liquid surface of the contents (reaction liquid) in the separable flask using a dropping funnel. 36.38 g of hydrochloric acid (20 ° C.) was added dropwise over 3 minutes. One minute and ten seconds after the start of the dropping of the hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, after adding 20.71 g of an aqueous 8 mol / l (20 ° C.) sodium hydroxide solution to the liquid surface of the contents in the separable flask, the contents in the separable flask were dropped using a dropping funnel. To the liquid surface, 24.02 g of 6 mol / l (20 ° C.) hydrochloric acid was added dropwise over 2 minutes.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain 13.28 g of nicotinic acid crystals. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 1, the volume-based average diameter was 20.4 μm.

[Comparative Example 4]
In a 500 ml separable flask (reaction vessel) equipped with three retreating blades (stirrer) having a radius of 23 mm, 20.02 g of nicotinic acid, 28.49 g of an 8 mol / l (20 ° C.) aqueous sodium hydroxide solution, and 300.31 g of water Was added to completely dissolve nicotinic acid to obtain a solution (raw solution) of the raw material organic acid salt.

  Subsequently, the stirring rotation speed of the three retreating blades was set to 300 rpm, and 6 mol / l (at the internal temperature of 5 ° C.) was applied to the liquid surface of the contents (reaction liquid) in the separable flask using a dropping funnel. 36.16 g of hydrochloric acid (20 ° C.) was added dropwise over 3 minutes. One minute and ten seconds after the start of the dropping of the hydrochloric acid, rapid crystal precipitation was visually observed.

  Subsequently, the reaction solution in the separable flask was filtered under reduced pressure and dried under reduced pressure to obtain 14.10 g of nicotinic acid crystals. Next, when the volume-based average diameter of the crystal was measured by the same laser diffraction type particle size distribution analyzer as in Example 1, the volume-based average diameter was 18.4 μm.

  The present invention relates to a method for crystallizing an organic acid, which comprises producing a crystal having a large average particle size and bulk density by adding an acid to a solution of an organic acid salt, and a crystallization apparatus suitable for the method. As described above, the filtration work is facilitated and has various usefulness. Therefore, the present invention can be used not only in the production of organic acids, but also in various chemical industries such as pharmaceutical manufacturing, organic chemical manufacturing, food manufacturing, and industrial chemical manufacturing such as additives using organic acids as raw materials. It is.

It is a schematic diagram which shows the structure of the crystallization apparatus used for the crystallization method of this invention. It is a schematic diagram which shows the structure of another crystallization apparatus used for the crystallization method of this invention.

Explanation of reference numerals

1 crystallizer 2 reaction vessel (crystallization reactor)
3 Acid supply line (acid supply means)
4 Base supply line (base supply means)
5 stirrer 7 acid storage tank 8 connecting pipe 9 connecting pipe 10 dropping pipe 12 base storage tank 13 connecting pipe 14 connecting pipe 15 dropping pipe 20 crystallizer 21 first reaction vessel 22 stirrer 31 second reaction vessel 32 stirrer 40 acid Supply line (acid supply means)
41 acid storage tank 42 connecting pipe 43 connecting pipe 44 drip pipe 50 base supply line (base supply means)
51 base storage tank 51 acid storage tank 52 connecting pipe 53 connecting pipe 54 dropping pipe 60 reaction liquid circulation line (reaction liquid circulation means)
61 Suction tube 62 Connection tube 63 Connection tube 67 Suction tube 68 Connection tube 69 Connection tube

Claims (9)

  A method for crystallizing an organic acid comprising adding a base to an organic acid crystal-containing liquid to convert a part of the organic acid crystals into an organic acid salt and dissolving the same, and adding an acid to the organic acid salt solution. .   By adding an acid to the solution of the organic acid salt, at least a part of all the organic acid crystals to be precipitated is precipitated, and by adding a base to the liquid containing the organic acid crystals, the precipitated organic acid is added. A method for crystallizing an organic acid, comprising converting a part of an acid crystal into an organic acid salt, dissolving the acid salt, and adding an acid to a solution of the organic acid salt. A method for crystallizing an organic acid, comprising adding an acid to a solution of an organic acid salt and crystallizing the organic acid,
After the organic acid starts to crystallize due to the addition of the acid, the base is added to the solution containing the organic acid crystal to convert a part of the organic acid crystal into an organic acid salt and dissolve it. A method for crystallizing an organic acid, the method comprising:   The addition of the acid and the addition of the base are performed in separate reaction vessels provided in communication with each other while circulating the liquid in the reaction vessel between the reaction vessels, and the solution of the organic acid salt before the initial acid addition. The amount (g) of the organic acid salt therein is P, the value obtained by dividing the molecular weight of the organic acid salt by the number of anionic functional groups contained in one molecule of the organic acid salt is Z, and the amount (g) of the base added is the equivalent of the base. (G) divided by M, addition time T (min), circulating amount of the solution per unit time F (ml / min), and logarithmic average of the maximum and minimum liquid volumes in the system as L (Ml), the amount of the base is adjusted so that the value of the formula represented by L × M / (T × F × P × Z) satisfies 0.5 or more and less than 1.5. 3. The method for crystallizing an organic acid according to item 3. The method for crystallizing an organic acid according to any one of claims 1 to 4, wherein the following M / (PxZ) satisfies the following expression.
Q / (P × Z) −0.3 ≦ M / (P × Z) ≦ Q / (P × Z) −0.03
M: value obtained by dividing the amount of base added (g) by equivalent (g) of the base Q: value obtained by dividing the amount (g) of acid added before base addition by the equivalent (g) of the acid P ： Amount of organic acid salt in solution of organic acid salt before initial acid addition (g)
Z: value obtained by dividing the molecular weight of the organic acid salt in the organic acid salt solution before the initial acid addition by the number of anionic functional groups contained in one molecule of the organic acid salt   The method for crystallizing an organic acid according to any one of claims 1 to 5, wherein the amount of the organic acid crystals remaining after the addition of the base is in the range of 1 to 30% by weight of the total crystals precipitated.   A step of obtaining an organic acid crystal using the method for crystallizing an organic acid according to any one of claims 1 to 6, and isolating the organic acid crystal from a reaction solution containing the organic acid crystal obtained by the step. And a method for producing an organic acid crystal.   A crystallization reaction vessel, an acid supply means for supplying an acid into the crystallization reaction vessel, and a base supply means for supplying a base into the crystallization reaction vessel, wherein the acid supply means and the base supply means, A crystallization apparatus, comprising supplying an acid and a base to positions separated from each other in the crystallization reaction vessel.   A first reaction vessel equipped with an acid supply means, a second reaction vessel equipped with a base supply means, communicating the first reaction vessel and the second reaction vessel, and A liquid circulating means for circulating the reaction liquid between the second reaction vessel and the crystallization apparatus.

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