JP2001055381A - Production of 1-benzylhydantoin crystal - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject crystal with slight impurities or the like, useful as an intermediate, for medicaments, agrochemicals and photographs, by maintaining a solution containing a specific benzylhydantoin within a plural- stage temperature range, and cooling the thus maintained solution to effect crystallization in high separability from the solution. SOLUTION: This crystal is obtained by preferably subjecting an aqueous solvent (e.g. water) solution containing 1-benzylhydantoin with a concentration of preferably 4 to 15 wt.%, more preferably 5-10 wt.%, to an activated carbon treatment and maintaining the thus treated solution within at least two-stage temperature range (preferably two-stage of 50 to 70 deg.C and <=30 deg.C), and cooling the thus maintained solution to effect crystallization therefrom.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing 1-benzylhydantoin crystals, and more specifically, to suppress the occlusion of impurities and the like from a solution containing 1-benzylhydantoin and to crystallize the solution. It relates to a manufacturing method. 1-Benzylhydantoin is used as a useful intermediate for medicines, pesticides, photographs and the like.

[0002]

2. Description of the Related Art As a method for producing 1-benzylhydantoin, for example, (1) a method in which an aqueous solution of potassium cyanate is added dropwise to an aqueous solution of N-benzylglycine hydrochloride, followed by cyclization with concentrated hydrochloric acid [Acta Acad. Abo. ,
Ser. B, 27 (6), 18pp. (1967)],
(2) a method of reacting N-benzylaminoacetonitrile, an alkali metal cyanate salt and an acid, and subjecting this to a heat treatment in the presence of an acid (JP-A-6-100543);
(3) A method of reacting an N-substituted-N-alkoxycarbonylaminoacetonitrile with a hydroxide selected from alkali metal and alkaline earth metal hydroxides, followed by treating with an acid (JP-A-10-72446). Gazette) is known.

In the literature (1), the number of reaction steps is large in order to obtain the N-benzylglycine salt as a raw material, and the purity and coloration of 1-benzylhydantoin obtained due to the large amount of inorganic salts are problematic. Remains. In the gazette of (2), crystallization is performed by cooling the reaction solution to obtain crystals, but the purity, properties and the like are not described and details are unknown.
Further, in the publication of (3), 1-benzylhydantoin is exemplified, but the examples relate to other hydantoins and do not describe crystals of 1-benzylhydantoin. 1-Benzylhydantoin is industrially usually treated as a crystal, and is often used as a drug,
In order to use it as a useful intermediate such as a pesticide or a photograph, it is preferable to purify it by recrystallization or the like, and there is no literature describing recrystallization conditions in detail. Examples of crystallization of hydantoin compounds other than 1-benzylhydantoin include recrystallization from ethanol (JP-A-4-198172), recrystallization from ethyl acetate (JP-A-1-299276),
Only recrystallization from water (JP-A-55-94373) is known. The present inventor has proposed that
An attempt was made to obtain crystals of benzylhydantoin, but the following problems became apparent.

[0004]

Since the crystal has poor separability between the crystal and the solution, the effect of cleaning the impurities by the solution is inferior and the purity of the obtained crystal is low; water and solvent in the crystal before drying are low. Is high, and it is difficult to remove adhering water and solvent by drying.
Among the above problems, particularly low purity is a problem as a photographic intermediate which is also a main use of the present compound, and other than that, improvement is required from an industrial and economic viewpoint.

[0005]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that a solution containing 1-benzylhydantoin is cooled at two or more temperature ranges and crystallized to form a crystal and a solution. The above problem was solved by producing a crystal having good separability and containing few impurities and the like.

[0006] That is, the present invention provides a method for producing 1-benzylhydantoin crystals, characterized in that a solution containing [1] 1-benzylhydantoin is crystallized by maintaining the solution in two or more temperature ranges and cooling. The production method, [2] the method for producing 1-benzylhydantoin crystals according to [1], wherein the solution containing 1-benzylhydantoin is treated with activated carbon, and [3] a solution containing 1-benzylhydantoin. Is a solution of an aqueous solvent, the method for producing 1-benzylhydantoin crystals according to the above [1] or [2], wherein the temperature range of two or more stages is 5
(1) The temperature of (1) to (3), wherein the temperature is in two stages of 0 to 70 ° C. and 30 ° C. or lower.
-Method for producing benzylhydantoin crystals, [5] concentration of solution containing 1-benzylhydantoin is 4% by weight or more
The method for producing 1-benzylhydantoin crystal according to any one of [1] to [4], wherein the amount is 15% by weight. Hereinafter, the present invention will be described in detail.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION A 1-benzylhydantoin crystal according to the present invention can be prepared by reacting a reaction solution containing 1-benzylhydantoin produced by a reaction or a solution in which 1-benzylhydantoin crystal is dissolved in a solvent in two or more temperature ranges. And crystallization.
At this time, the method of obtaining the reaction solution containing 1-benzylhydantoin or the 1-benzylhydantoin crystal used is not particularly limited, and a known method can be employed. As the solvent, an aqueous solvent is preferably used. In general, water is used as the aqueous solvent. In addition to water, an inert organic solvent (eg, tetrahydrofuran; acetone; acetonitrile; alcohols such as methanol and ethanol) can be used. These can be used alone or as a mixture of two or more as needed. Preferably, it is water or a mixed solvent with water.

The concentration of 1-benzylhydantoin is not particularly limited as long as it is dissolved.
It is preferably 15% by weight, more preferably 5% by weight to 10%.
% By weight. If the concentration of 1-benzylhydantoin is low, it is not economical, and if it is high, the obtained effect is reduced. In some cases, it becomes oily without crystallization and separates from the solvent, affecting the purity and drying efficiency. When the solution containing 1-benzylhydantoin is treated with activated carbon as needed, it is preferable to carry out the treatment under acidic conditions. Further, it is preferable to carry out the reaction at a pH of about 1 to about 4. For adjusting the pH, any acid can be used if it has no problem in the process, equipment, etc.
Generally, an inorganic acid or an organic acid can be used, and sulfuric acid and nitric acid are preferably used. The amount of the acid used is not particularly limited.

The treatment temperature may be any condition under which no crystals are precipitated. To increase the productivity, the concentration of the 1-benzylhydantoin solution is increased, preferably from about 70 to about 110.
C, more preferably in the range of about 90 to about 100C.
The pressure for the treatment is not particularly limited, and the treatment can be usually performed under normal pressure (standard atmospheric pressure). The processing time is not limited, and usually 1 to 4 hours is sufficient. The activated carbon to be used may be any commonly used one, and a commercially available product can be used. The activated carbon treatment may be performed in any of a tower system and a batch system, but the tower system is preferred from the viewpoint of operation.

[0010] Cooling during crystallization is preferably performed in a temperature range of two or more stages. More preferably, the first stage is about 50 to about 7
The temperature is preferably set in a two-stage temperature range of 0 ° C. and a second stage of about 30 ° C. or less. The crystallization may be a batch type or a continuous type, but a continuous type is advantageous industrially. If the crystallization temperature is too high, the crystal recovery rate will be low, and if it is too low, the purity will be reduced. The crystallization time varies depending on the apparatus, the concentration of the solution, and the like. For example, in the case of performing a continuous process, a 1-benzylhydantoin solution having a temperature of about 90 ° C. or higher is sent to a first crystallization tank kept at a temperature of about 50 ° C. to about 70 ° C. for a certain time (about 1 to about 6 ° C.). After holding for about 2 hours, this can be achieved by sending the solution to a second crystallization tank maintained at about 30 ° C. or lower, for example, about 20 ° C. to about 30 ° C. The pressure at the time of crystallization is not particularly limited, and it can be usually carried out under normal pressure. The bulk specific gravity of 1-benzylhydantoin crystal is determined according to JIS
It carried out by the measuring method according to K6721-66.

[0011]

EXAMPLES The present invention will now be described specifically with reference to examples and comparative examples, but the present invention is not limited to these examples. The absorbance described in this example is 1.0% by weight.
A methanol solution containing the crystals of
315 nm wavelength with methanol as reference cell in mm cell
It is the value when measured in. This wavelength is an absorption band in which 1-benzylhydantoin does not show absorption, and is an absorption band of impurities. Therefore, the absorbance has a positive correlation with the purity of 1-benzylhydantoin, and serves as an index of the purity. A high-purity crystal is a crystal in which the amount of impurities is defined, and has an absorbance of 0.05 or less.

(Example 1) 1-benzylhydantoin crystal 61 synthesized by the method disclosed in JP-A-6-100543
5 g was completely dissolved in 8200 ml of water (about 95 ° C). This solution was adjusted to pH 2.5 with sulfuric acid, and activated carbon was
g was added and kept at about 95 ° C. for 30 minutes. Subsequently, the activated carbon was removed by hot filtration, and the obtained filtrate was cooled to about 60 ° C., whereby crystals were slightly generated. After leaving at about 60 ° C. for 30 minutes, it was cooled to about 25 ° C. and left for 2 hours for crystallization.
The precipitated crystals were centrifuged to obtain wet crystals. The water content of the obtained wet crystals was measured and found to be 3.9% by weight.
Subsequently, drying (temperature 110 ° C., 2 hours) results in 5
40 g of granular 1-benzylhydantoin crystals were obtained.
The measured bulk specific gravity and absorbance of the dried crystals were 0.70 and 0.020, respectively. Further, when the obtained 1-benzylhydantoin crystal was subjected to X-ray crystal diffraction, the face spacing d (Å) of the peaks was 6.34, 5.65, and 5.
Characteristic peaks were found at 48, 4.38, 4.21, 3.35, and 3.19. FIG. 1 shows an X-ray diffraction diagram. The numbers in the figure correspond to the numbers in Table 1. Conditions: X-ray source; Cu-Kα ray, output: 50 kV, 18
0 mA, scan; θ / 2θ method, step; 5 ° / mi
n, measurement range 10-90 °, experimental error of surface spacing; d ±
0.02 FIG. 2 shows an infrared absorption spectrum of the crystals measured by the KBr tablet method.

[0013]

[Table 1]

Example 2 An aqueous solution of 1-benzylhydantoin was prepared in the same manner as in Example 1, and the aqueous solution was cooled to about 60 ° C. without being treated with activated carbon. As a result, crystals were slightly generated. After leaving at about 60 ° C. for 30 minutes, it was cooled to about 25 ° C. and left for 2 hours for crystallization. The precipitated crystals were centrifuged to obtain wet crystals. The water content of the obtained wet crystals was measured and found to be 7.5% by weight. Then, dry (temperature 110 ° C, 4
535 g of scaly 1-benzylhydantoin crystals were obtained. The bulk specific gravity and absorbance of the dried crystals were 0.45 and 0.045, respectively. When the obtained crystal was subjected to X-ray crystal diffraction, the peak spacing d (Å) 5.57, 5.37, 4.31, 3.69,
Characteristic peaks were found at 3.36 and 2.94. FIG.
The X-ray diffraction diagram is shown in FIG. The numbers in the figure correspond to the numbers in Table 2. FIG. 4 shows an infrared absorption spectrum of the crystals measured by the KBr tablet method.

[0015]

[Table 2]

Reference Example 1 Approximately 95
A 1-benzylhydantoin aqueous solution at a temperature of 0 ° C was prepared. The solution was adjusted to pH 2.5 with sulfuric acid, and 15 g of activated carbon was added.
Incubated at about 95 ° C for 0 minutes. Subsequently, activated carbon was removed by hot filtration, and the obtained filtrate was rapidly cooled to about 25 ° C (25 ° C).
(30 minutes at 25 ° C. for 60 minutes), and 1-benzylhydantoin crystals were precipitated. The crystals were centrifuged in the same manner as in Example 1, and the moisture content of the obtained wet crystals was measured to be 7.8% by weight. Then dry (temperature 1
By carrying out (10 ° C, 4 hours), 538 g of flaky crystals were obtained. The bulk specific gravity and absorbance of the dried crystals were 0.47 and 0.048, respectively. Further, when the obtained crystal was subjected to X-ray crystal diffraction, the plane spacing d (ピ ー ク) of the peaks was obtained.
5.57, 5.37, 4.31, 3.69, 3.36,
A characteristic peak was found at 2.94. FIG. 5 shows an X-ray diffraction diagram. The numbers in the figure correspond to the numbers in Table 3.

[0017]

[Table 3]

[0018]

As described in detail above, one of the present inventions
In the method for producing -benzylhydantoin crystals, high-purity crystals could be provided by crystallizing the solution containing 1-benzylhydantoin while suppressing the absorption of impurities. In the production method of the present invention, a high-purity crystal can be provided by providing a temperature range of two or more stages for crystallization, and a granular high-purity crystal having a high bulk specific gravity can be provided by using activated carbon treatment. Can be provided.

[0019]

[Brief description of the drawings]

FIG. 1 is a drawing showing an X-ray diffraction pattern of a 1-benzylhydantoin crystal of the present invention obtained in Example 1. The vertical axis indicates the diffraction intensity, and the horizontal axis indicates the diffraction angle.

FIG. 2 is a drawing showing an infrared absorption spectrum of the 1-benzylhydantoin crystal of the present invention obtained in Example 1. The vertical axis shows transmittance (%), and the horizontal axis shows wave number (cm ^-1 ).

FIG. 3 is a drawing showing an X-ray diffraction pattern of 1-benzylhydantoin crystal obtained in Example 2.

FIG. 4 is a drawing showing an infrared absorption spectrum of the 1-benzylhydantoin crystal obtained in Example 2.

FIG. 5 is a drawing showing an X-ray diffraction pattern of 1-benzylhydantoin crystal obtained in Reference Example 1.

Claims (5)

[Claims] 1. A method for producing a 1-benzylhydantoin crystal, comprising cooling a solution containing 1-benzylhydantoin in two or more temperature ranges, cooling the solution, and crystallizing the crystal. 2. The method according to claim 1, wherein the solution containing 1-benzylhydantoin is treated with activated carbon.
-A method for producing benzylhydantoin crystals. 3. The method for producing 1-benzylhydantoin crystals according to claim 1, wherein the solution containing 1-benzylhydantoin is a solution of an aqueous solvent. 4. The temperature range of two or more stages is 50 to 70 ° C.
The method for producing a 1-benzylhydantoin crystal according to any one of claims 1 to 3, wherein the temperature is in a two-stage temperature range of 30C or lower. 5. The method for producing 1-benzylhydantoin crystals according to claim 1, wherein the concentration of the solution containing 1-benzylhydantoin is 4% by weight to 15% by weight.