JP3266395B2 - Crystallization method of organic chemicals - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a crystallization method for cooling an organic chemical solution to precipitate crystals of the organic chemical dissolved in the organic chemical solution.

[0002]

2. Description of the Related Art In the production of industrial chemicals, pharmaceuticals, foods, and the like, a crystallization step is provided in order to ensure the quality of a final product because a sufficient purification effect cannot be obtained by solution purification.

The conventional crystallization method used in this crystallization process is shown in FIG. 3 as a graph of a solubility curve.
The crystallization operation line in FIG. 3 is schematically shown, but as shown in this figure, conventionally, an organic chemical was dissolved in a good solvent to form an organic chemical solution, which was then cooled to lower the liquid temperature. To generate bulk crystals beyond the metastable region and the flat crystal region,
The organic chemical solution was cooled so as to pass through the bulk crystal region as it was to precipitate bulk crystals.

The bulk crystal has a crystal structure suitable for production because solid-liquid separation in the next step is easy and the crystallization speed is high. However, since the crystal is heavy, it is of a Faudler type as shown in FIG. With a small stirring blade 2, the precipitated bulk crystals cannot be floated, and the supersaturation inside the tank 4 becomes non-uniform as shown in FIG. 6A, and as shown in FIG.
In the upper portion of the tank 4 having a higher degree of supersaturation, a large amount of fine needle crystals having poor filtration properties are finally deposited, and a slurry having extremely poor fluidity is generated (FIG. 6B).

In order to prevent this, a large stirring blade such as an anchor type shown in FIG. 4 is used, which has a high stirring efficiency, can make the degree of supersaturation in the tank 4 uniform, and can precipitate only bulk crystals. 6 requires an apparatus dedicated to crystallization, which imposes great restrictions on equipment that can be used for crystallization.

[0006]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above-mentioned circumstances, and it is possible to obtain a crystal having good filtration properties and a slurry having good fluidity even with low stirring efficiency.
Accordingly, it is an object of the present invention to provide a crystallization method capable of performing crystallization excellent in production suitability even with a general-purpose device.

Another object is to provide a method for obtaining crystals which can be easily taken out using a general-purpose kettle having a Faudler blade which can also be used for reaction and concentration, without using an anchor blade with high efficiency stirring. is there.

[0008]

Means for Solving the Problems As a result of intensive studies and studies to achieve the above object, the present inventor has found that by depositing a flat crystal, crystallization excellent in manufacturing suitability can be performed even in a general-purpose apparatus. Was found.

That is, according to the first aspect of the present invention, an organic chemical is dissolved in a good solvent to obtain an organic chemical solution.
Later, a uniform solution with the good solvent is formed in this organic chemical solution.
That the poor solvent was added slowly, the start of crystallization step of adjusting, primarily flat crystallization degree of supersaturation of the organic chemicals solution is deposited, provided subsequent to the start of crystallization step, the saturated solubility of the organic chemical solution A crystallization step of lowering the temperature of the organic chemical solution while changing the solvent composition so as to lower the temperature, and mainly continuing the precipitation of flat crystals. Through the crystallization step, there is provided a method of crystallizing an organic chemical, in which a crystal of the organic chemical is precipitated by stirring the organic chemical solution so that the flow of the deposited flat crystal is completely suspended.

The present invention is a very effective method for purifying the produced organic chemical in the final step of producing the organic chemical. Examples of the organic chemicals to which the method of the present invention is applied include cyan couplers, magenta couplers, coloring agents for ordinary photographs represented by yellow couplers, coloring materials for instant photographs, antifoggants, and the like. Not limited, low melting point (mp is preferably 0 to 50 ° C)
Is widely applicable.

According to the method of the present invention, first, the degree of supersaturation of the organic chemical solution is adjusted so as to mainly deposit flat crystals (crystallization start step). This adjustment may be performed by any method.For example, after dissolving an organic chemical in a good solvent to form an organic chemical solution, gradually add a poor solvent to the organic chemical solution.
In addition to the above, there is a method of adjusting the degree of supersaturation of the organic chemical solution so as to mainly deposit flat crystals.

Here, "predominantly flat crystals are precipitated" or "mainly keep flat crystals deposited" means that the flat crystals occupy 60% or more, preferably 80% or more of the precipitated crystals.

A good solvent and a poor solvent are terms well known to those skilled in the art, and a good solvent means a solvent having a high ability to dissolve a solute, and a poor solvent has a small ability to dissolve a solute.
Or a solvent having almost no such ability. Typically,
A solvent that dissolves 5 g or more, preferably 20 g or more of the solute in 100 g of the solvent at 40 ° C. is a good solvent, and a solvent that dissolves the solute in 10 g or less of the solvent in 100 g of the solvent, preferably 1 g only, is a poor solvent.

Ethyl acetate is a good solvent for many photographic reagents. Similarly, methanol, ethanol, and water are poor solvents. In the present invention, two kinds of poor solvents can be used in combination.
The poor solvent to be used in combination can be added sequentially, or can be mixed in advance and used. A combination that forms a uniform solution even after the addition of the poor solvent is preferable.

The supersaturation degree of the organic chemical solution is 3 or more and 3 or more.
It is preferable to adjust so as to be 0 or less. here,
Supersaturation refers to the ratio of the absolute value of the solution concentration to the saturation concentration.

Next, according to the method of the present invention, the temperature of the organic chemical solution is lowered while changing the solvent composition so as to lower the saturation solubility of the organic chemical solution, and the filterability and the stirring property are mainly reduced. The precipitation of a good flat crystal is continued (crystallization step). The saturation solubility of the organic chemical solution may be reduced by any method.For example, water is added to an organic chemical solution whose supersaturation is adjusted by adding a poor solvent to an organic chemical solution using a good solvent as a solvent. A method of changing the solvent composition in a homogeneous system by gradually adding the solvent is mentioned.

The precipitated flat crystals are stirred in a completely suspended state throughout the crystallization start step and the crystallization step so that the degree of supersaturation of the organic chemical solution in the apparatus does not become uneven.
The term “completely suspended” as used in the text means that crystals are located at the bottom of the tank.
It means a stirring state that does not stay for 2 seconds or more.

In carrying out the crystallization method of the present invention on a large scale, appropriate stirring conditions can be determined based on the stirring conditions of a crystallization experiment using a small-scale experimental apparatus. For example, Motonaga et al., "Effect of stirring on particle size analysis in crystallization of phenoxyacetic acid compound" (Chemical Engineering Transactions No. 1).
(Vol. 0, No. 2, published in 1984) is effective. In this method, a minimum stirring condition that satisfies the complete suspension condition obtained under the condition of being scaled down geometrically similar is first determined. Next, the stirring rotation speed under the scaled-up condition can be determined so that the value of the Z factor becomes the same.

Hereinafter, the present invention will be described with reference to Examples.
They are only examples, and the present invention is not limited thereto.

[0020]

【Example】

Example 1 First, in order to extract a crystal of a cyan coupler (1) having the following structural formula I, the method of the present invention was carried out in a flask experiment.

[0021]

Embedded image As an experimental device, a separable flask having a flask diameter of 80 mm and 500 ml and a small Faudler blade having a stirring blade of 45 mm were used.

Into the separable flask containing 43 ml of ethyl acetate, 79 g of the cyan coupler (1)
And then heated to 40 ° C. to dissolve. Then
192 ml of methanol (poor solvent) was added to this solution at a liquid temperature of 4.
While maintaining the temperature at 0 ° C., the mixture was gradually added with stirring. Further, seed crystals were added to the solution, 213 ml of water (another poor solvent) was added with stirring, and the temperature was lowered to 20 ° C. over 4 hours. In this process, flat crystals are seen to precipitate, and the precipitated flat crystals are completely suspended.
The stirring speed was adjusted. The stirring rotation speed at this time is 400 rpm
m. In addition, the temperature starts to decrease from 40 ° C
Until the supersaturation was 20-25.

After the temperature reached 20 ° C., the stirring was continued for 1 hour, and the temperature was rapidly lowered to 5 ° C. to secure the crystallization yield.

The slurry thus formed had a good fluidity. Next, the crystallized product and the mother liquor were separated by filtration.

The crystallized product was a flat crystal of 5 μm × 30 μm, and the crystallization yield was 92%. The above crystallization method was applied to the production.

The pot used was made of 4000 liter glass lining, and the stirring blade was a Faudler type stirring blade having a blade diameter of 900 mm. FIG. 1 shows a schematic configuration of a crystallizer 20 provided with this kettle and stirring blades.

The crystallization apparatus 20 includes the above-described kettle 22 and the above-described stirrer 24 having three Faudler blades (rod-shaped blades).
And a baffle 26 having a generally F-shaped cross section inclined upward. An opening 22B is formed substantially at the center of the ceiling 22A of the kettle 22, and the Faudler blades of the agitator 24 are held in the kettle 22 via the opening 22B. The rotation speed of the stirrer 24 is 95 rpm at the maximum and 27 at the minimum.
A variable speed of rpm can be achieved. Ceiling 22A
The baffle 26 is also held in the shuttle 22 through the opening 22C through the opening 22C. Around the side wall 22D and the bottom surface 22E of the shuttle 22,
A cooling tank 28 for cooling the solution in the kettle 22 is formed.
A cooling liquid inlet 28A for entering the cooling liquid and a cooling liquid outlet (not shown) for discharging the cooling liquid 30 are formed. The coolant inlet 28A and the coolant outlet are connected to a heat exchanger (not shown) via a pipe (not shown), and the coolant 30 circulates between the heat exchanger and the cooling tank 28. The bottom surface 22E of the shuttle 22
A discharge port 22 </ b> F for discharging a slurry obtained by cooling the solution is formed at a substantially central portion of the, and the discharge of the slurry is adjusted via a valve 32. The crystallization apparatus 20 includes a solution port for injecting the solution into the other kettle 22 and a thermometer for measuring the temperature inside the kettle 22. The clearance between the stirring blades of the stirrer 24 and the deepest central portion of the bottom of the kettle is 80 mm, so that the crystals staying at the bottom can be easily floated.

In this embodiment, brine is used as the cooling liquid. 780 kg of the above-mentioned cyan coupler (1) was charged into the kettle 22 charged with 426 liters of ethyl acetate, and then dissolved while stirring while keeping the liquid temperature at 40 ° C. Next, 1919 liters of methanol was gradually added to the solution with stirring while maintaining the solution temperature at 40 ° C. Further, a seed crystal was added to this solution, and 2132 liters of water was added with stirring, and the temperature was lowered to 20 ° C. over 4 hours. The flat crystals precipitated in this process were adjusted to a stirring speed that was a condition of complete suspension. This stirring speed is
It was 48 rpm. After the temperature reached 20 ° C., stirring was maintained for 1 hour, and the temperature was rapidly lowered to 5 ° C., and then the crystals and the mother liquor were separated by filtration using a centrifuge.

At this time, the slurry had good fluidity, and the crystallized product obtained was a flat crystal similar to that of the flask.

FIG. 2 shows a solubility curve and a schematic crystallization operation line. The solubility curve shown by a broken line in the figure represents the solubility curve of the solution before the addition of the poor solvent, and is shown by a solid line. The solubility curve represents the solubility curve after the addition of the poor solvent, and the solubility curve shown by the broken line is lowered to the solubility curve shown by the solid line to facilitate the crystallization operation in the flat crystal region.

Example 2 Even when the cyan coupler (2) having the following structural formula II was crystallized under the same scale-up conditions as in Example 1, flat crystals with good filterability could be obtained. .

[0032]

Embedded image Example 3 Even when the cyan coupler (3) having the following structural formula III was crystallized under the same scale-up conditions as in Example 1, a flat crystal with good filterability could be obtained.

[0033]

Embedded image Example 4 Even when a magenta coupler intermediate having the following structural formula IV was crystallized under the same scale-up conditions as in Example 1, flat crystals with good filterability could be obtained.

[0034]

Embedded image

[0035]

By using the method for crystallizing organic chemicals according to the present invention, it is possible to obtain a crystal having good filtration properties and a slurry having good fluidity even if the stirring efficiency is low. In addition to performing excellent crystallization, it is possible to establish a scale-up method that can be applied to experimental equipment from manufacturing equipment.

[Brief description of the drawings]

FIG. 1 is a schematic configuration diagram of a crystallization apparatus of the present invention.

FIG. 2 is a diagram showing a model of crystal form control in the crystallization method of the present invention.

FIG. 3 is a diagram showing a model of crystal form control in a conventional crystallization method.

FIG. 4 is a view showing a state of crystallization in a conventional crystallization method, wherein (A) shows a state in which a bulk crystal has begun to precipitate,
(B) shows the state at the end of crystallization.

FIG. 5 is a diagram showing a model of crystal form control when a Faudler type stirring blade is used in a conventional crystallization method.

FIG. 6 is a view showing a state of crystallization when a Faudler-type stirring blade is used in a conventional crystallization method, and FIG.
Shows the state where the bulk crystals started to precipitate, and (B) shows the state at the end of the crystallization.

[Explanation of symbols]

 Reference Signs List 20 crystallizer 22 pot 24 stirrer (Faudler type) 28 cooling layer

Claims (2)

(57) [Claims] An organic chemical is dissolved in a good solvent to dissolve the organic chemical.
Liquid and then add the good solvent and a homogeneous solution
Was slowly added a poor solvent to form a crystallization initiation step of adjusting, primarily flat crystallization degree of supersaturation of the organic chemicals solution is deposited, provided subsequent to the start of crystallization step of the organic chemical solution While changing the solvent composition so as to lower the saturation solubility, the temperature of the organic chemical solution is lowered, and a crystallization step for mainly continuing the precipitation of flat crystals is provided. A method of crystallizing an organic chemical, characterized in that the organic chemical solution is stirred so that the flow of the precipitated flat crystals is completely suspended during the crystallization step. 2. A crystallization method of the organic chemicals of claim 1, wherein the degree of supersaturation after the adjustment is 3 or more and 30 or less.