JPH0119366B2 - - Google Patents

Description

[Detailed description of the invention]

In the present invention, a liquid mixture consisting of an impurity substance and a target substance is first subjected to temperature crystallization to remove a part of the impurity substance in a liquid phase, and the mixture having an increased concentration of the target substance is further subjected to pressure crystallization. In particular, it relates to a method for recovering target substances with high purity and high yield. Attempts have been made for a long time to recover target substances with high purity and high yield from eutectic compounds in which impurities and target substances form eutectics, but in general, improvements in purity and recovery rate have been made. are considered to be contradictory demands that are difficult to satisfy both at the same time, and there is a relationship in which when points are placed on purity, recovery rate is sacrificed, and when points are placed on recovery rate, purity is sacrificed. Ta. In particular, since conventional crystallization mainly relied on temperature manipulation,
It is difficult in itself to perform delicate temperature control with high precision.If you try to make the inside of the system uniform and perform high precision control, the speed of temperature rise or cooling will become infinitely slow, which is a real problem. It is impossible to completely prevent temperature gradients within the system, and once formed, it is impossible to eliminate them in a short period of time. Compared to the conventional pressure crystallization method, the control range is extremely narrow and the purity and recovery rate are significantly inferior. That is, regarding the basics of pressure crystallization method, for example, Japanese Patent Publication No. 53-22065;
43053, 50-104771, 51-81783, 54-
As already disclosed in numerous patent application specifications such as No. 28272 and No. 54-52676, delicate pressure control is easy, and pressure increases and decreases are completed instantly.
It has advantages such as uniform pressure distribution in the system and no temperature distribution, and it has become possible to some extent to satisfy both purity and yield through expanded control range and high-precision control. . However, it is generally difficult to increase the size of equipment for pressure crystallization, and because it is smaller than temperature crystallization equipment, the throughput per process is unavoidably small. . Therefore, in order to specifically develop the pressure crystallization method in industrial applications, it is necessary to improve the processing efficiency to satisfy economic efficiency, and it is also desirable to further improve the recovery rate and purity. As a result, we have repeatedly considered the issue from various perspectives. The present invention was made as a result of such studies, and is a purification method that can recover a target substance with high purity and high yield while satisfying an economical basis when applied to industrial applications. It is intended for the purpose of providing. That is, the purification method of the present invention that has achieved the above object is a skillful combination of temperature crystallization method and pressure crystallization method, and includes the following two routes. The first route is to subject a liquid mixture (hereinafter referred to as liquid mixture A) consisting of a target substance and substantially one or more impurities to preliminary crystallization in a temperature range higher than the eutectic temperature of the impurity and target substance. After the crystallization concentrates the target substance exclusively on the solid phase side and impurities on the liquid phase side, a part of the liquid phase is discharged, and as a result, the initial liquid mixture A has a solid phase fraction. and intermediate slurry mixture B with high target substance concentration.
However, this is then pressurized in a pressure vessel with an overfunction, and when the solid phase fraction further increases and the concentration of the target substance in the liquid phase decreases, the liquid discharge line of the pressure vessel is connected to the outside of the vessel. The liquid phase is discharged by communicating with the atmosphere on the low pressure side of the pressure vessel, and then the remaining mixture in the pressure vessel is compressed to lower the liquid phase pressure, and the melt generated by partially melting the crystal surface is removed. The gist is to discharge the solid matter with a high concentration of the target substance in the pressure vessel by discharging it together with the liquid phase. In the second route, since the temperature of the intermediate slurry mixture B has decreased, the next pressure crystallization will be performed at a lower temperature side, which may lead to a decrease in purity. The gist of this method is to raise the starting temperature of pressure crystallization by raising the temperature to a temperature at which all of the solid phase does not melt, and then perform pressure crystallization according to the first route. That is, the main point of the present invention is to remove impurities in liquid mixture A by
This method is relatively simple and can be carried out in large quantities by temperature crystallization, which removes a certain amount of substance and increases the target substance concentration in the raw material mixture to be subjected to pressure crystallization, thereby improving the economical efficiency of the equipment. The efficiency is high and the recovery rate of the target substance is extremely high.
In the second route, pressure crystallization is performed at a relatively high temperature, so the concentration of the target substance in the recovered product is extremely high. The structure and effects of the present invention will be explained below based on drawings and specific examples of refining operations.
Figure 1 is an explanatory diagram showing the entire process flow.
The figure shows the case of the second route, but if the first route is adopted, the melting can 5 is omitted and the concentrating can 3 is
is directly connected to the pressure crystallizer 6. In other words, 1 in the figure
is a stock solution tank in which the liquid mixture A mentioned above is stored and sent to the temperature crystallizer 2 by a pump _P1 . Here, the stirring blade 8 operated by the motor M is immersed, and a cooling mechanism (not shown) is added to cool the mixture to a temperature slightly higher than the eutectic point of the target substance and impurity. Therefore, the liquid mixture A in the crystallizer 2 is cooled and stirred, and the target substance is precipitated. That is, in this method, a substance with a high melting point is purified as a target substance. Therefore, a slurry is formed in the crystallizer 2 and then transferred to the concentrator 3.
The slurry is concentrated by gravity sedimentation or any other method. In the figure, gravity sedimentation is used, so the layer is separated into a sedimentation zone and a supernatant layer.The sedimentation zone, which contains a large amount of the target substance and has a high solid phase concentration, is sent to pressure crystallization, and the supernatant layer, which has a high concentration of impurities, is pumped. P ₂ to drain tank 4. In other words, since the solid phase already contains the target substance at a fairly high concentration, it is naturally subjected to the next pressure crystallization, but since the liquid phase also contains a large amount of uncrystallized target substance, it is necessary to discard it. Only a portion is sent to the liquid tank 4, and the majority is used as a raw material for pressure crystallization together with the solid phase. In other words, since preliminary crystallization of the target substance has been performed in the above-mentioned process, the amount of impurities in slurry B, which is the target of pressure crystallization, has been considerably reduced, and the equipment economy of the pressure crystallizer has been reduced. sex becomes extremely high. However, as is obvious from the above explanation, if the amount of liquid fed to the drain tank 4 becomes too large, the target substance will be discharged along with the liquid, and the recovery rate of the target substance will deteriorate. It is recommended that the amount fed to the liquid tank 4 be adjusted by comprehensively considering the concentration of the liquid mixture A, the degree of cooling in the crystallizer 2, the capacity of the pressure crystallizer 6, etc. Slurry B with a high solid phase concentration taken out from the bottom of the concentrator 3 would be supplied as is to the pressure crystallizer 6 if it were the first route described above, but it would be brought to a considerably lower temperature by temperature crystallization. Therefore, if this is brought as it is to the pressure crystallizer 6 and pressure crystallized, the pressure crystallization will occur on the low temperature side (close to the eutectic temperature) and the concentration of the target substance in the solid phase will decrease. There is a problem that there is a relative decline in Therefore, as shown in the second route, it is recommended to immediately inject the solid phase into the melting can 5 to dissolve part or all of the solid phase before feeding it to the pressure crystallizer 6. In other words, the above-mentioned temperature crystallization is carried out not for the direct purpose of crystallizing the target substance, but for the purpose of discharging as much impurity as possible in the liquid phase. After the purpose is achieved by discharging a part of the liquid phase, the whole is made into a uniform liquid phase (or the liquid phase is made to such an extent that some seed crystals remain),
It is more rational to obtain high-purity crystals of the target substance by subjecting it to pressure crystallization. However, if we take into account the energy consumption required for the heat source for remelting, if we recover even a small amount of the temperature that has fallen due to temperature crystallization, we can obtain a commensurate effect, so the heating in the melting can 5 It can even be said that it is more rational to suppress this to a necessary and sufficient level. Therefore, generally speaking, it is desirable to install a slurry pump as pump P ₃ , and it is preferable to install a slurry pump as pump P 3.
The slurry-like mixture whose solid phase fraction has been slightly reduced is fed into the high pressure chamber 8 from the bottom of the pressure crystallizer 6. Although the configuration of the pressure crystallizer 6 itself does not limit the present invention, the bottom cover 9 and the cylindrical side wall 1 are shown in the figure.
0, a top lid 11, and a pressing piston 12, the bottom lid 9 is formed with a liquid injection part and a liquid discharge filter 14, a liquid discharge line connected to the filter 14 is provided with a valve 15, and a liquid tank 7
connected to. Further, a product extrusion piston 16 is provided next to the side wall 10, and a piston 18 is further attached to the outer surface of the side wall 10 via a pedestal 17. Therefore, when the slurry mixture is injected into the high pressure chamber 8, the piston 12 descends, the pressure within the high pressure chamber 8 increases, and pressure crystallization is performed. When the crystallization of the target substance has sufficiently progressed to obtain the solid substance B, the valve 15 is opened and the liquid in the chamber 8 is discharged into the tank 7, but when the liquid phase is discharged, the liquid in the high pressure chamber 8 The liquid phase, which was the pressure medium, disappears and the system is communicated with the low pressure side outside the system via the solid phase, so the pressure inside the high pressure chamber 8 begins to decrease. Therefore, for example, JP-A-54-
As already disclosed in No. 159378, etc., the solid phase surface portion with a high impurity content ratio partially melts and a liquid phase is generated. Therefore, in this state piston 1
When B is further lowered, the remaining solid phase is compressed, and the pressure inside the high pressure chamber 8 further decreases and approaches atmospheric pressure, while the solid B is partially melted and compressed, and finally the high pressure As the pressure inside the chamber 8 becomes equal to the atmospheric pressure, the target substance purity of the solid material B becomes extremely high, and the liquid phase is also sufficiently discharged. Then, when the piston 18 is pulled up, the side wall 10
As the high pressure chamber 8 is released, the piston 16 is moved forward and the solid material B is taken out of the system. Next, the piston 16 is retracted, the piston 18 is lowered,
By sequentially raising the piston 12, the pressure crystallizer 6
Purification was carried out by assembling and repeating each of the above operations, and the purity of the target substance in the thus obtained solid B was extremely high, and the recovery rate of the target substance was also good. Next, a mixture of m-cresol and p-cresol (hereinafter each component is called M-form and P-form, and the mixture is M/P
We conducted purification experiments using the first route and the second route, and obtained certain results, so we will clarify the results for each. For convenience of explanation, the second route will be described first. A stock solution with a weight ratio of P and M isomers of 70/30 (P/
M-body: 40℃) to 3.5℃ (P-body and M-body's eutectic point is 2.5
℃) to precipitate a small amount of solid phase. Part of the liquid phase is discharged from here and the 80/20 P/M body (3.5
℃), and heated this slurry to 15℃ to determine the solid phase fraction.
After adjusting the concentration of P substance in the liquid phase to 0.2585 (0.7303), it was injected into a pressure crystallizer and pressurized to 1500 atmospheres. The temperature change and solid phase fraction change associated with the pressure change were as shown in Table 1.

[Table] Next, open the valve 15 and remove the solid matter B in the high pressure chamber 8.
was continued to be squeezed, and the target substance was obtained according to the procedure described above. Regarding the temperature change at this time, the change in the residual solid phase fraction in the container, the change in the P content in the container, etc.
It was as shown in the table.

[Table] As seen in Table 2, the P fraction of the final solid obtained was 0.9970, compared to the first route (Table 4) and the comparative example (Table 6) described below. The purity of the P-isomer was extremely high, and the degree of purification as a P-isomer was sufficiently satisfactory. Also, the residual solid phase fraction in the container (ratio when the stock solution is 1) is 0.4854, and the recovery rate is lower than the result of the first route, but comparative example (Table 6)
This is extremely high compared to , and can be fully satisfied. Next, we will show an experimental example of the first route. In this experiment, we use a stock solution with a weight ratio of P and M isomers of 70/30 (40°C) as in the previous experiment, and cool it to 3.5°C to solidify it. After precipitating a small amount of the phase, a portion of the liquid phase was removed to obtain an 80/20 P/M body (3.5°C), and this slurry was directly subjected to pressure crystallization without heating. Thereafter, the same procedure was repeated, and the results shown in Tables 3 and 4 were obtained. Table 3 corresponds to Table 1, and Table 4 corresponds to Table 2. As seen in these results, the recovery rate was extremely high due to the low temperature during pressure crystallization, but the The purity of the solid matter was slightly inferior.

【table】

[Table] Next, a comparative example is shown. In this case, since the preliminary crystallization temperature was 10°C, the amount of solid crystallized at this stage was small (solid phase fraction: 0.0913). Therefore, the discharge of the liquid phase may lead to a large loss of P-bodies.
The discharge of the liquid phase had to be abandoned. Therefore, preliminary crystallization has no more than the meaning of seed crystal precipitation, and the progress of subsequent similar treatments is shown in Table 5 (Tables 1 and 3).
As shown in Table 6 (corresponding to Tables 2 and 4), the purity of P-isolate in the final solid product was 99.5%, which was not that bad. The residual solid phase fraction was significantly lowered to 0.3269, and only slightly poor results were obtained in terms of final product purity and significantly in terms of recovery rate.

【table】

[Table] Figure 2 shows the operation diagram for the pressure crystallization part in each of the above experiments. The curve showing 100% is the solid-liquid equilibrium curve when the P isomer is 100%. In the first and second routes described above, an essential step of the present invention is performed in which a portion of the liquid phase is discharged when a small amount of the solid phase is precipitated by preliminary cooling. Therefore, the purity of P-form in each method was 98.9% and 99.7%, and the recovery rate was 65.4% and 48.5%. On the other hand, in the comparative example, the purity was 99.5% because the above essential steps were missing, but the recovery rate was 32.7%.
When the target purity, which is almost the same as that of the second route, was achieved, the recovery rate was only about 2/3.
In this way, preliminary cooling crystallization is performed before pressure crystallization,
Draining part of the liquid phase from the resulting solid-liquid mixture has been shown to be a very effective measure.
It goes without saying that improving the recovery efficiency within the pressure crystallizer is extremely significant in improving the operating efficiency of the device. Since the present invention is configured as described above, excellent results can be obtained in terms of both purity and recovery rate in separating target substances, and impurity substances can be preliminarily separated in terms of equipment economy. Therefore, it has become possible to effectively utilize the pressure crystallizer.

[Brief explanation of drawings]

FIG. 1 is an explanatory diagram of the flow of the present invention, and FIG. 2 is an operation diagram. 1... Raw solution tank, 2... Temperature crystallizer, 3... Concentrator, 4... Drainage tank, 5... Melting can, 6... Pressure crystallizer.

Claims (1)

[Claims] 1. A method for separating and purifying a target substance to a high purity from a liquid mixture in which substantially one or more impurities coexist with the target substance, the method comprising:
Preliminary crystallization is performed in a temperature range that does not fall below the eutectic point of the impurity and the target substance to increase the solid phase fraction of the target substance and increase the concentration of the impurity in the liquid phase. After further increasing the solid phase fraction by discharging a portion of the liquid phase from the mixture, the solid-liquid mixture is pressurized in a pressure vessel with an overfunction, so that the solid phase fraction further increases and becomes liquid. When the concentration of the target substance in the phase has decreased, the liquid discharge line of the pressure vessel is connected to the low-pressure side atmosphere outside the vessel to discharge the liquid phase, and then the remaining mixture in the pressure vessel is squeezed while the liquid phase is removed. A substance characterized in that the pressure is lowered and the melt generated by partially melting the crystal surface accompanying this is discharged together with the liquid phase, leaving the solid with a high concentration of the target substance in the pressure vessel. High purity purification method. 2. A method for purifying a substance to high purity according to claim 1, wherein the liquid mixture is a mixture of m-cresol and p-cresol. 3. A method for purifying a substance to high purity according to claim 2, wherein m-cresol is the main impurity and p-cresol is the target substance. 4. A method for separating and refining a target substance to high purity from a liquid mixture in which substantially one or more impurities coexist with the target substance, the method comprising:
Preliminary crystallization is performed in a temperature range that does not fall below the eutectic point of the impurity and the target substance to increase the solid phase fraction of the target substance and increase the concentration of the impurity in the liquid phase. After further increasing the solid phase fraction by discharging a portion of the liquid phase from the mixture, raising the solid-liquid mixture to a temperature at which a portion of the solid phase melts;
This is then pressurized in a pressure vessel with an overfunction, and when the solid phase fraction further increases and the concentration of the target substance in the liquid phase decreases, the liquid discharge line of the pressure vessel is connected to the low pressure side outside the vessel. The liquid phase is discharged by communicating with the atmosphere, and the remaining mixture in the pressure vessel is further compressed to reduce the liquid phase pressure, and the melt generated by partially melting the crystal surface is mixed with the liquid phase. A method for purifying a substance to high purity, characterized by discharging solid matter having a high concentration of the target substance and leaving it in a pressure vessel. 5. The method for purifying a substance to high purity according to claim 4, wherein the liquid mixture is a mixture of m-cresol and p-cresol. 6. A method for purifying a substance to high purity according to claim 5, wherein m-cresol is the main impurity and p-cresol is the target substance.