JP2919660B2 - Method for producing crystal of L-α-aspartyl-L-phenylalanine methyl ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an L-α-aspartyl-L-
The present invention relates to a method for crystallizing phenylalanine methyl ester.

[0002]

2. Description of the Related Art L-α-aspartyl-L-phenylalanine methyl ester (hereinafter abbreviated as APM) is a substance which is expected to be widely used as a low-calorie sweetener because of its good sweetness. . As a method for industrially producing this APM, various methods have been known up to now. In any of these production methods, in order to isolate APM from the reaction solution and obtain it as a product, The crystallization step is essential.

In this crystallization step, for example, the crude product is usually dissolved again in water, an organic solvent or a water-containing organic solvent, and is subjected to heat exchange with a refrigerant or reduced pressure using a crystallizer equipped with stirring blades. A method of cooling by evaporating a part of the solvent to precipitate crystals, and then filtering and dehydrating the crystals with a centrifuge or the like is employed. Further, the APM aqueous solution having a certain concentration or more is cooled by conduction heat transfer so as to become an apparent frozen dessert-like pseudo-solid phase without giving forced flow such as mechanical stirring or the like. A method for obtaining crystals by cooling is also known.

However, in a conventional crystallizer equipped with a stirrer, for example, an APM obtained by a crystallizer equipped with a paddle-type or turbine-type stirrer has a fine needle-like crystal habit. Solid-liquid separation properties in filtration and dehydration were extremely poor, and there was a great problem in practical use.

When the solid-liquid separation operation is repeated,
There is also a problem that the base layer of the cake is consolidated and solidified, and it takes a lot of manpower and time to remove it.In this case, even in the drying step following the crystallization step, the water content of the cake becomes large and the drying load increases, Moreover, the bulk specific gravity of the obtained dry powder also increases, and handling becomes extremely difficult.

Further, a method using only conduction heat transfer for cooling without stirring the system requires an extremely long operation time, so that it is not a method which can be implemented industrially at all.

[0007]

SUMMARY OF THE INVENTION It is an object of the present invention to find a method for crystallizing APM having good handleability from a solution in a filtration operation or a dehydration operation.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide an APM.
Was solved while stirring in a crystallizer of a specific configuration when crystallizing from the solution.

The specific crystallizer is defined in claim 1. Roughly speaking, a plate for sweeping the tank and the bottom of the tank, and a bar-shaped member provided on the tank and extending in the vertical or horizontal direction, respectively. And a baffle plate.

In the present invention, APM is crystallized while stirring the APM solution using a specific crystallizer defined in claim 1.

A plurality of baffles are provided along the axial direction from the lower part to the upper part on the inner peripheral wall surface of the crystallization tank. The APM solution that can be handled covers a wide range of concentrations. For example, the concentration of APM in the form of an aqueous solution may be 2% by weight to an aqueous solution having a saturation solubility, preferably 3.5 to 4.0% by weight. it can.

[0012] The crystallization temperature is from 80 ° C to 0 ° C, preferably
The range is from 60 ° C to 5 ° C. In crystallizing APM, the peripheral speed of the stirring blade is set to 0.1 to 1.2 m.
/ Sec, preferably in the range of 0.3 to 0.6 m / sec.

The crystallization liquid may be cooled by a method of providing a jacket outside the tank and circulating a refrigerant, a method of vacuum evaporation, or a combination thereof.

The stirring blade used in the present invention will be described.

The stirring blade is provided on a rotating shaft provided at the center of the tank.
Mounted on one side of the wing. As a matter of course, an odd number of sheets other than 1 may be used as long as the rotation of the shaft is smoothly performed, but about two sheets are provided symmetrically from the viewpoint of ease of machining. The first member constituting the wing is essentially a plate, which sweeps the bottom of the vessel. It is preferable that the distance between the lower end of the plate and the tank bottom is narrow. The reason is not clear,
It seems that it is preferable that the liquid flow toward the tank bottom does not increase.

The end facing the inner wall of the tank is preferably at a certain distance from the inner wall. This is for forming a liquid flow toward the inner wall.

The second member is a substantially rod-shaped member extending from the rotation shaft provided on the first member to the inner wall of the tank, in other words, an arm extending from the rotation shaft. This member is not limited to a single member, and may be arranged in large numbers vertically. The limitation of the length is the same as that of the length of the first member, and may be shorter. The direction in which the rod-shaped member extends does not have to be particularly parallel to the liquid surface, but may be inclined so long as it is provided so as to substantially cut the liquid horizontally.

The third member is a rod or a plate-like member which extends substantially vertically in the liquid and stirs the liquid. If the mechanical strength for stirring the liquid can be maintained, the first member or the second member can be used. It may be fixed to only one of them.
The direction of this member also does not require strictness, and may be substantially vertical. The first member or the second member is moved so as to move across the liquid flow from the inner wall of the tank in the direction of the rotation axis. What is necessary is just to be provided through. This member may also be plural.

The above-mentioned three members are most usually provided in the same plane, and constitute a lattice-like member having a space with one plate as a whole. It does not matter even if it forms a single twisted curved surface.

FIGS. 1 to 5 show examples of possible blade shapes in the present invention, and FIGS. 6 to 8 are not used in the present invention.

The second member and the third member will be described. In the above description, words such as parallel to the liquid surface and cutting the liquid sideways are used, but for the sake of simplicity of explanation, this is expressed on the assumption that the liquid surface is intentionally stationary. ing. However, if the wings rotate in the tank, the liquid at the bottom of the tank inevitably flows in the tank from the center to the outer periphery, and in response to this, the liquid in the tank rises at the outer periphery and drops at the center tool. Convection occurs and circulates. If the circulating flow becomes intense, the liquid level will form a paraboloid with the center part down. If so, the second member and the third member follow the paraboloid and change their direction, as shown in FIG. 3, and the second member and the third member are integrated into FIG. As shown, it may be a single curved bar.

According to the method of the present invention, crystals having good filterability can be obtained while stirring the crystallization liquid. That is, APM crystals continue to precipitate and maintain good fluidity of the liquid, and the obtained crystals have good operability in subsequent steps such as transport, separation and drying, and are extremely strong against physical impact. It is.

Further, although the crystallized crystal usually adheres to the heat transfer surface and causes so-called scaling, which often involves very difficult removal, the crystallization of APM according to the method of the present invention does not. It is extremely easy to separate and drop the crystal layer from the cooling surface.

According to the present invention, APM crystals having good filterability can be obtained, so that not only the solid-liquid separation properties of the product but also the crystallization time can be shortened to reduce the size of the apparatus and the load on the dryer. Reduction and remarkable improvement in workability in each step can be achieved. The method of the present invention is applied to APM containing impurities such as diketopiperazine (DKP), which is a cyclized product of APM, and L-α-aspartyl-L-phenylalanine.
Even when applied to a liquid, the APM containing no such impurities is reduced due to the reduction of the adhered mother liquor in solid-liquid separation and the improvement of cake washability.
Crystals can be obtained, and the present invention provides an APM crystallization process that is significantly economically advantageous.

In the conventional stirring blades shown in FIGS. 6 to 8, increasing the stirring speed decreases the size of APM crystals, and decreasing the stirring speed decreases the flow of the APM. Trouble occurs.

Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1 This example was performed using the crystallization apparatus shown in FIG. The crystallization tank is a cylindrical vertical type with an inner diameter of 700 mm and a height of 850 mm, a pot with a capacity of 300 liters, and having four baffles inside.

The stirring blade is D: 420 mm, H: 760 mm
Was used.

APM containing 3% DKP in the crystallization tank
250 liters of a raw material solution dissolving 5 kg (60 ° C., A
(The initial concentration of PM is 3.6% by weight), the rotation speed of the stirring blade is set to 30 rpm, the refrigerant at 10 ° C. is circulated through the jacket 7, and the operation is always cooled from the inside of the solution, that is, by a vacuum pump. The inside of the crystallization tank was crystallized under the reduced pressure for adjusting the degree of vacuum together with the temperature. About 40 minutes after the start of the test, crystals began to precipitate in the solution. The solution temperature at this time was 40 ° C. One hour later, the entire solution was filled with crystals. Thereafter, the mixture was cooled to 7 ° C. by circulating a 0 ° C. refrigerant.
The crystallization was completed 3 hours after the start of the test.

When the slurry thus obtained was filtered and dewatered by a centrifuge, the water content of the cake became 40% after 20 minutes. The obtained amount was 12.5 kg (wet), the recovery rate was 80%, and the DKP content was 0.1%.

Comparative Example 1 In Comparative Example 1, a stirring blade shown in FIG. 6, that is, a flat blade turbine type blade of D = 400 mm was provided in the crystallization tank used in Example 1. The crystallization was performed in the same manner as in Example 1. However, due to the properties of the stirring blade, the rotation speed was set to 100 rpm. During the crystallization, a portion where the slurry did not flow occurred, and a large amount of adhered to the inner wall at the time of discharge. Even after 2 hours or more for the subsequent filtration and dehydration, the water content was 60% or more. In addition, there was filtration leakage, and the recovery rate was 60%.

Example 2 The same stirring blade as in Example 1 (D; 420 mm, H; 760 m)
m), and the APM aqueous solution is the same as in Example 1, but
Cooling crystallization was performed by circulating a jacket refrigerant under normal pressure at a rotation speed of the stirring blade of 50 rpm. The temperature of the refrigerant was set at 10 ° C. until crystals were deposited,
The crystallization was completed at 7 ° C by circulating a refrigerant at 7 ° C. The crystallization time was about 4 hours.

The slurry thus obtained was filtered and dehydrated by a centrifugal separator.
After 40 minutes the cake moisture is 40% and the yield is 12.5 kg
(Wet), the recovery was 80%.

Incidentally, Although all of the above examples were performed by batch operation, industrially, continuous operation is also possible.

Example 3 This example was performed using the crystallization apparatus shown in FIG. The crystallization tank is a cylindrical vertical type with an inner diameter of 700 mm and a height of 850 mm.
A boiler with a capacity of 300 liters and a baffle plate inside
There is one.

Stirrer blade: D: 400 mm, H: 750 mm
Was used.

The crystallization operation was carried out in the same manner as in Example 1. When the obtained slurry was filtered and dehydrated by a centrifugal separator, the water content of the cake became 38% after 20 minutes. The yield was 13.1 kg (wet) and the recovery was 80%.

Example 4 This example was performed using the crystallization apparatus shown in FIG. The crystallization tank is a cylindrical vertical type having an inner diameter of 700 mm and a height of 850 mm, a pot with a capacity of 300 liters, and having four baffles inside.

Stirrer blade: D: 400 mm, H: 760 mm
Was used.

The crystallization operation was performed in the same manner as in Example 1. When the obtained slurry was filtered and dewatered by a centrifugal separator, the water content of the cake was reduced to 42% after 20 minutes. The yield was 11.9 kg (wet) and the recovery was 80%.

[0041]

As is clear from the above description and Examples, the present invention has the following advantages in the step of crystallizing and separating APM. (1) No special device other than the stirring blade is required, and a normal cylindrical vertical kettle can be used.

(2) The slurry containing APM crystals obtained by the method of the present invention requires less time for solid-liquid separation than that obtained by the conventional method.

(3) Since the separability of the crystal is remarkably good, the washing effect is enhanced and a product with less impurities can be obtained.

(4) The load in the drying step is reduced. And the handling property of the powder after drying is good.

[Brief description of the drawings]

FIG. 1 is a cross-sectional view of a crystallization apparatus provided with a specific stirring blade used for carrying out the present invention.

FIG. 2 is a cross-sectional view of a crystallization apparatus provided with a specific stirring blade used for carrying out the present invention.

FIG. 3 is a cross-sectional view of a crystallization apparatus provided with a specific stirring blade used for carrying out the present invention.

FIG. 4 is a cross-sectional view of a crystallization apparatus provided with a specific stirring blade used for carrying out the present invention.

FIG. 5 is a cross-sectional view of a crystallization apparatus provided with a specific stirring blade used for carrying out the present invention.

FIG. 6 is a view showing a shape of a stirring blade not used for carrying out the present invention.

FIG. 7 is a view showing a shape of a stirring blade not used for carrying out the present invention.

FIG. 8 is a view showing a shape of a stirring blade not used for carrying out the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 1st member 2 2nd member 3 3rd member 4 Rotating shaft 5 Crystallization tank 6 Stirrer blade 7 Jacket 8 Baffle plate

Continuation of front page (56) References JP-A-62-71521 (JP, A) JP-A-55-109403 (JP, A) JP-A-49-15681 (JP, A) JP-B-38-23929 (JP, A) , B1) JP 48-22893 (JP, B1) British Patent 1489028 (GB, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C07K 5/075 B01D 9/02 C07K 1/14

Claims (2)

(57) [Claims] 1. A method for crystallizing L-α-aspartyl-L-phenylalanine methyl ester from a solution thereof, comprising using a crystallizer equipped with wings and baffles having the structure specified below. Method with stirring. (A) At least one blade is fixed to the rotating shaft so that the liquid in the crystallization tank can be stirred. (B) The wing includes at least the following three members (c), (d) and (e). (C) It is substantially a flat plate, and is fixed to the rotating shaft at one lateral end of the plate, and the end facing the inner wall of the tank opposite to the fixed end extends up to an arbitrary long distance from the inner wall, Downward is the first member that keeps a fixed short distance from the tank bottom. (D) provided on the liquid surface side of the first member, extending in a direction substantially parallel to the liquid surface between the rotation shaft and the tank inner wall in a plane substantially parallel to the first member, and having one end having a rotation shaft; A second member that is substantially rod-shaped and that extends from the inner wall of the tank to another arbitrarily long distance. (E) provided on the liquid surface side with respect to the first member, always fixed to one of the first member and the second member, and substantially up and down in a plane substantially perpendicular to the liquid surface; A third member in the form of a plurality of rods or plates extending to the third member. (F) A plurality of baffle plates are arranged on the side wall surface of the crystallization tank from the lower part to the upper part along the axial direction at intervals. 2. The method of claim 1, wherein the second member and the third member are integrally formed as a single rod including a substantially arcuate curved wing. thing.