JPH075518B2 - Method for crystallizing and refining β crystal of tetrakis [3- (3,5-ditertiary butyl-4-hydroxyphenyl) propionyloxymethyl] methane - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to tetrakis [3- (3,5-ditertiarybutyl-4-hydroxyphenyl) propionyloxymethyl] useful as an antioxidant for polyolefins and the like. Β for methane
The present invention relates to a crystallization purification method for industrially stably obtaining crystals.

[Problems to be Solved by Conventional Techniques and Inventions]

Tetrakis [3- (3,5-ditertiarybutyl-4-hydroxyphenyl) propionyloxymethyl] methane (hereinafter sometimes referred to as Compound I) is 3- (3,5-
Ditertiary butyl-4-hydroxyphenyl) propionic acid lower alkyl ester and pentaerythritol,
It is known from US Pat. No. 3,644,482 to be produced by transesterification in the presence of a base catalyst such as an alkali metal lower alkoxide.

Recent crystal structure studies on compound I have revealed that compound I has four types of crystals, α crystal, β crystal, γ crystal and σ crystal (US Pat. No. 4,405,807). Among them, as described in the U.S. patent specification, α crystals can be obtained only by the conventional method because the crystals cannot be agitated during the crystallization and thus the purity and the hue are both poor. I can't. Therefore, the β crystal is suitable as the crystal structure from the viewpoints of problems in the manufacturing method and handling as a product.

In producing β crystal, water is contained in an amount of 2 to 10% by weight with respect to a water-soluble solvent of methanol or ethanol,
European Patent Publication No. 244361 discloses a method in which the transesterification reaction product is dissolved, clarified and filtered if necessary, and then cooled to gradually lower the temperature. However, in this method, when the crystallization liquid is gradually cooled, the crystal structure is partially changed to an α crystal which is not preferable from the viewpoint of handling as a product as described above, or the slurry is formed even after crystallization. If kept stirring, the crystal structure changes from β crystal to α crystal over time. in this way,
With the crystallization method described in the European Patent Publication, it is extremely difficult to obtain β crystals stably with good industrial reproducibility. In addition, it is extremely difficult to industrially produce β-crystals in view of the fact that the crystal structure changes to α-crystals when β-crystals are stored in a wet state at room temperature. .

An object of the present invention is to provide an industrially advantageous method for stably obtaining Compound I as β crystal.

[Means for Solving the Problems]

In order to solve the above problems, as a result of intensive studies, the present inventors have found that in order to stably produce β crystal on an industrial scale, the compound I was dissolved in a solvent under reflux and melt-mixed, and then cooled in a specific solvent. The inventors have found that the intended purpose can be achieved by a crystallization refining method in which the mixture is poured and mixed and rapidly cooled, and the present invention has been completed. That is, the present invention is directed to tetrakis [3- (3,5-di-di-tertiary carboxylic acid obtained by transesterification of pentaerythritol and lower alkyl 3- (3,5-ditertiary-butyl-4-hydroxyphenyl) propionic acid. Three
Secondary butyl-4-hydroxyphenyl) propionyloxymethyl] methane-containing reaction mixture is melt mixed in a water-soluble solvent under reflux, and then 0.2 to 1.5 based on the reaction mixture.
0.06 to 10 times the weight of the water-soluble solvent and the water-soluble solvent
Tetrakis [3-] characterized in that a cooled solvent consisting of 0.09 weight times of water and the above melt-mixed liquid are mixed and crystallized, and the β crystal structure generated by adding water is stabilized. The present invention relates to a crystallization purification method of (3,5-ditertiary butyl-4-hydroxyphenyl) propionyloxymethyl] methane.

The compound I-containing reaction mixture used in the present invention may be used as it is as an ester exchange reaction product, or may be a residue (often a candy-like product) obtained by concentrating and removing the solvent used for improving fluidity in the catalyst removal step. ) May be used.

According to the method of the present invention, a water-soluble solvent (methanol, ethanol or a mixed solvent thereof, etc.) is added to such a transesterification reaction mixture itself or to a residue obtained by concentrating and removing the solvent used for improving fluidity in the catalyst removal step. ) Is added and melt-mixed under reflux, and seed crystals of β crystal are added to the transesterification reaction product in a cooled solvent consisting of a water-soluble solvent (methanol, ethanol or a mixed solvent thereof) and water, if necessary. Preferably, 0.05 to 1% by weight is added, and the above melt-mixed liquid is poured into and mixed with it to crystallize, and further water is added to stabilize the β crystal produced, and the crystal produced Can be isolated, and if necessary, washed and dried to obtain a compound I having a single crystal structure of β crystal.

The amount of the water-soluble solvent used for the melt mixing under reflux is 0.1 to 1 times by weight, preferably 0.4 to 0.6 times by weight, of the reaction product containing the compound I. The temperature at which mixing is started may be a temperature at which the reaction product containing the compound I melts in the water-soluble solvent, and is usually 100 to 150 ° C, preferably 120 to 130 ° C. The solution after mixing is kept at the temperature at which the solvent refluxes. The holding time is the time until it is dissolved, and it is set within 2 hours. When it is held for a longer time, a small amount of α crystal is precipitated, and becomes a seed crystal after pouring and mixing, which causes the α crystal to be mixed. The recrystallization solvent used, that is, a solvent consisting of a water-soluble solvent and water, is 0.2 to 1.5 times by weight of the reaction product containing the compound I and 0.06 to 0.09 of the water-soluble solvent. It is preferably composed by weight of water, and is usually kept cooled at 0 to 30 ° C, preferably 15 to 25 ° C. This recrystallization solvent was poured and mixed with the liquid melt-mixed under reflux in the water-soluble solvent obtained as described above,
Crystals are precipitated at 10 to 50 ° C, preferably 35 to 45 ° C. Furthermore, by adding water to the crystallized solution of the β crystal thus obtained, the β crystal of the compound I can be industrially stably obtained without changing the crystal structure thereafter.
The advantage of adding water is that, in addition to improving the stabilization of the β crystal structure, the crystallization yield is improved because the solubility is lower than the original solubility of the solvent, and as a result of further mixing with water, ignition and explosion It is industrially preferable because it can improve the safety against The amount of water to be mixed is usually 0.2 times or less by weight, preferably 0.1 to 0.2 times by weight, with respect to the total amount of the water-soluble solvent used, and if it exceeds 0.2 times by weight, product quality such as purity and hue is significantly reduced. Tend to do. The addition of water may be carried out temporarily, or continuously or intermittently.

[Operation and effect of the invention]

The method of the present invention is a crystallization purification method from a heterogeneous solution,
According to the method of the present invention, a granular β crystal is stably industrially produced without changing the crystal structure of Compound I.

The granular compound I obtained by the method of the present invention is a white granular compound having excellent properties such as high bulk specific gravity and high fluidity. In addition, analysis using differential scanning calorimetry (DSC) (in the analysis by differential scanning calorimetry, the endothermic melting peak center of α crystal shows 121 ~ 123 ℃, β crystal shows 113 ~ 115 ℃, crystal structure of The change can be clearly seen from the X-ray diffraction spectrum.), Which shows an endothermic melting peak having only one center at 113 to 115 ° C. and an X-ray (Cu-Kα) diffraction spectrum, U.S. Pat. No. 4,405,807. As described in the book as the characteristic of β crystal, it has been confirmed that it has a single crystal structure of β crystal because it has five peaks in the diffraction angle 2θ of 5 ° to 10.6 °. The obtained β crystal stably maintains its crystal structure. In the conventional method, the compound I was colored and the β crystal structure was changed to the α crystal structure, which was difficult to industrially manufacture, but in the present method, the apparatus was scaled and pulverized. As a white crystal with excellent hue without any inconvenience such as inability to stir, it is sufficiently satisfactory for practical use in terms of purity, and the compound can be easily and stably produced as a β crystal on an industrial scale. It became possible to do.

〔Example〕

Hereinafter, the present invention will be specifically described by reference examples, examples and comparative examples. However, the present invention is not limited to those exemplified here.

Reference Example 1 500 m equipped with stirrer, cooler, thermometer and nitrogen inlet pipe
182.7 g of methyl 3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionate (0.625
Mol) and pentaerythritol 18.9 g (0.139 mol)
Then, 0.73 g (0.0035 mol) of monobutyltin oxide is added, the temperature is raised to 185 ° C. and the reaction is carried out for 1 hour, and the produced methanol is distilled off. Then, nitrogen gas was bubbled into the liquid under reduced pressure of 60 to 70 mmHg (2NL / HV), and the reaction was continued for 13 hours to complete the reaction. [The amount of tri-substituted product (A) whose esterification reaction has not been completed in the mixture at the end of the reaction is 5% or less (HPLC (S / S)].) Excess 3- (3,5-ditertiary butyl-4-hydroxy Phenyl) methyl propionate at 150-185 ℃, 0.5-0.2mmHg
Under the condition, thin film distillation was carried out in 1 hour. The amount of the distillate was 19.5 g, and the distillate rate was 97%. This product can be used as it is in the next reaction.

Then, the reaction mixture was cooled to 115 ° C., nitrogen gas was introduced, the pressure was returned to atmospheric pressure, and the mixture was uniformly dissolved in toluene.

This toluene solution was washed with 400 g (0.16 mol) of 5% oxalic acid water, and subsequently aqueous separation was repeated twice with 40 g of water at 60 ° C. The toluene layer was concentrated at 125 ° C., 30 mmHg, for 1 hour to give tetrakis [ A pale yellow candy-like substance consisting of 3- (3,5-ditertiary butyl-4-hydroxyphenyl) propionyloxymethyl] methane was obtained.

Example 1 100 g of the candy-like substance obtained in Reference Example 1 was mixed with 125 g of methanol.
The mixture was gradually added from 0 ° C, and melt-mixed under reflux (68 ° C).
Subsequently, the recrystallization solvent consisting of 92.5 g of methanol and 7.5 g of water was cooled to 20 to 25 ° C., 0.1 g of seed crystals were added, and then,
When the above melt was added while stirring, the internal temperature became 42 ° C. Then, after stirring for 1 hour at an internal temperature of 35 to 45 ° C. to precipitate crystals, 17.6 g of water is added, stirred for 1 hour, cooled to 20 ° C., kept stirred for 48 hours, and centrifuged. The separated product was dried to obtain 83 g of granular white crystals having a bulk specific gravity of 0.57.
This compound showed only one endothermic melting peak centered at 114.5 ° C in DSC analysis. This means that crystals are β
It supports that the crystals are single (Fig. 1). Also, X
It was confirmed by the X-ray (Cu-Kα) diffraction spectrum that it had a β crystal structure (FIG. 2). The melting point measured using a melting point measuring device with a microscope was 111 to 115 ° C, and the crystal purity analyzed by liquid chromatography was 98% or more.

Example 2 50 g of the candy-like substance obtained in Reference Example 1 was used, the solvent was changed to ethanol, and the amount of solvent and water used was 1/2 that of Example 1.
The same operation as in Example 1 was carried out to obtain 41 g of granular crystals having a bulk specific gravity of 0.52. This compound has a center of 11 in the DSC analysis.
It showed only one endothermic melting peak at 4 ° C. This supports that the crystal is single β crystal. Further, it was confirmed by an X-ray (Cu-Kα) diffraction spectrum that it had a β crystal structure. With a melting point of 112-115 ° C, the crystal purity analyzed by liquid chromatography is 98% or more.

Example 3 1 to 4 equipped with a stirrer, a cooler, a thermometer, and a nitrogen introducing tube
In a neck flask, methyl 3- (3,5-ditertiarybutyl-4-hydroxyphenyl) propionate 671.6 g (2.3 mmol), pentaerythritol 68.0 g (0.50 mol), monobutyltin oxide 2.25 g (10.9 mmol). , Monobutyltin trichloride 0.16 g (0.57 mmol) (catalyst amount corresponds to 0.5 mol% of methyl propionate compound in total) and 100 g of toluene were charged, and 170 to 1 was added with stirring.
The reaction was carried out at 75 ° C for 12 hours. During the reaction, 500 g of toluene was added dropwise and the methanol produced was distilled off. After the reaction was completed, 200 g of toluene was added and dissolved, and 5 wt% oxalic acid water was added.
After adding 200 g and stirring for 1 hour, the mixture was allowed to stand and the aqueous layer was separated and removed. The organic layer was washed twice with 200 g of water, and toluene was distilled off under reduced pressure to give tetrakis [3- (3,5-ditertiary butyl-
4-hydroxyphenyl) propionyloxymethyl]
590 g of a candy containing methane was obtained.

The same operation as in Example 1 was performed for 100 g of this candy-like substance,
81 g of white granular crystals having a bulk specific gravity of 0.55 were obtained. This compound is DSC
The analysis showed only one endothermic melting peak centered at 114 ° C. This supports that the crystal is single β crystal. In addition, β by X-ray (Cu-Kα) diffraction
The crystal structure was confirmed, the melting point was 110 to 114 ° C., and the crystal purity (analysis by liquid chromatography) was 98% or more.

The bulk specific gravity and the repose of the β crystals of tetrakis [3- (3,5-ditertiarybutyl-4-hydroxyphenyl) propionyloxymethyl] methane obtained in Examples 1, 2 and 3 are shown in Table 1 below. The corners are shown in comparison with a commercial product.

From the above, it can be seen that the product obtained by the present invention has better fluidity than the commercial product.

Comparative Example 1 25 g of methanol was added to 50 g of the candy-like substance obtained in Reference Example 1.
The mixture was gradually added from 0 ° C, and melt-mixed under reflux (68 ° C).
Next, the recrystallization solvent adjusted to 46.3 g of methanol and 3.8 g of water was cooled to 20 to 25 ° C., 0.1 g of seed crystals were added, and then the above solution was added under stirring to an internal temperature of 43 ° C. It was
Then, the mixture was stirred at an internal temperature of 35 to 45 ° C. for 1 hour to precipitate crystals, immediately cooled to 20 ° C., and continued to be stirred for 4 to 5 hours, and the crystals became fine powder, and stirring became impossible. The obtained crystals were filtered through a glass filter, washed and dried with methanol cooled to 20 ° C, and the melting point was measured to be 121 to 123 ° C. DSC analysis showed that the endothermic melting peak of α crystal (center 123.0).
(° C) was shown (Fig. 3). In addition, it was confirmed from the X-ray (Cu-Kα) diffraction spectrum that it had an α crystal structure (FIG. 4).

Comparative Example 2 3- (3,5-ditertiary butyl-4) was added to a 1000 ml four-necked flask equipped with a stirrer, a condenser for distillation, a thermometer, and a toluene inlet tube.
-Hydroxyphenyl) methyl propionate 200 g (0.68
Mol), pentaerythritol 21.2 g (0.15 mol) and di-butyltin oxide 1 g were charged, and the temperature was raised to 170 ° C. Toluene was continuously added dropwise, and the produced methanol was distilled off and maintained for 12 hours to complete the reaction. After completion of the reaction, toluene is added to dilute and di-butyltin oxide is removed to obtain a toluene solution. Toluene was distilled off to obtain 201 g of a pale yellow candy-like substance. Obtained candy-like substance 10
With respect to 0 g, the same procedure as in Comparative Example 1 was performed to precipitate crystals, immediately cool to 20 ° C., and continue stirring. After 1 hour, the crystals were finely divided and stirring became impossible. The obtained crystals were filtered through a glass filter, washed with methanol cooled to 20 ° C, and dried, and then the DSC was obtained at a melting point of 121 to 124.3 ° C.
The analysis showed an endothermic melting peak of α crystal (center 123.2 ° C). In addition, X-ray (Cu-Kα) diffraction spectrum shows α
It was confirmed to have a crystal structure of crystal.

Comparative Example 3 121.3 g of methanol was added to 50 g of the candy-like substance obtained in Reference Example 1.
The mixture was gradually added from 5 ° C, and melt-mixed under reflux (68 ° C). Then 3.8g of water was added dropwise and gradually cooled to obtain the internal temperature.
Crystals precipitated at around 55 ° C. Stir for 3 with further cooling
It continued for hours. The crystals obtained are filtered, washed with methanol, and dried, and the melting point is measured to be 110 to 124 ° C.
showed that. The results of DSC analysis are two endothermic melting peaks (α crystal peak center 122.4 ℃, β crystal peak center 113.8 ℃).
The ratio of α crystal to β crystal was 28:72 from the area ratio.

Comparative Example 4 The same operation as in Comparative Example 3 was carried out except that the stirring time in Comparative Example 3 was changed from 3 hours to 5 hours. The melting point of the obtained crystal was measured and found to be 111 to 125 ° C. X-ray (Cu-K
The α) diffraction spectrum is shown in FIG. In the DSC analysis,
Two endothermic melting peaks (α crystal peak center 122.2 ° C, β crystal peak center 113.8 ° C) were shown, and the ratio of α crystal to β crystal was 50:50 from the area ratio (Fig. 5).

Comparative Example 5 The same operation as in Comparative Example 3 was carried out, except that the stirring time in Comparative Example 3 was changed from 3 hours to 10 hours. The precipitated crystals became fine powder and could not be stirred. The melting point of the obtained crystal was measured and found to be 121 to 124 ° C. The result of the DSC analysis showed only one endothermic melting peak (center 122.8 ° C.), and the crystal structure was a single α crystal. Further, it was confirmed by X-ray (Cu-Kα) diffraction that the compound had an α crystal structure.

Comparative Example 6 When 50 g of the candy-like substance obtained in Example 3 was used and the same operation as in Comparative Example 5 was performed, the precipitated crystals were finely powdered and could not be stirred as in Comparative Example 5. The crystals thus obtained were separated by filtration, washed with methanol and dried, and the melting point was measured to show 119 to 123 ° C. DSC analysis showed an endothermic melting peak of α crystal (center 122.5 ° C). Further, it was confirmed by X-ray (Cu-Kα) diffraction that the compound had an α crystal structure.

Comparative Example 7 Example 1 except that the operation of melt mixing under reflux (68 ° C.) in Example 1 was performed at a temperature (63 to 65 ° C.) lower than the reflux temperature.
The same operation was carried out. The melting point of the obtained crystal was measured and found to be 110 to 125 ° C. The results of DSC analysis showed two endothermic melting peaks (α crystal peak center 123.0 ° C., β crystal peak center 114.0 ° C.), and the ratio of α crystal to β crystal was 20:80 from the area ratio.

Comparative Example 8 The same operation as in Example 1 was carried out except that in Example 1, the mixture was melt-mixed under reflux (68 ° C.) and the temperature was maintained for 4 hours. The melting point of the obtained crystal was measured and found to be 111 to 124 ° C. The results of DSC analysis showed two endothermic melting peaks (α crystal peak center 123.1 ° C, β crystal peak center 114.2 ° C), and the ratio of α crystal to β crystal was 35:65 from the area ratio.

[Brief description of drawings]

FIG. 1 and FIG. 2 show the analysis pattern of the product of Example 1 by differential scanning calorimetry and the X-ray (Cu-K
α) diffraction spectrum, FIGS. 3 and 4 show the analysis pattern and X-ray (Cu-Kα) diffraction spectrum of the product of Comparative Example 1 by differential scanning calorimetry, and FIGS. 5 and 6 respectively. 3 shows an analysis pattern and an X-ray (Cu-Kα) diffraction spectrum of the product of Comparative Example 4 by differential scanning calorimetry.

Claims (6)

[Claims] 1. Tetrakis [3- (3,5-di-primary) obtained by transesterification of pentaerythritol with 3- (3,5-ditertiary butyl-4-hydroxyphenyl) propionic acid lower alkyl ester. The tertiary-butyl-4-hydroxyphenyl) propionyloxymethyl] methane-containing reaction mixture is melt-mixed in a water-soluble solvent under reflux, and then 0.2 to 1.5 times by weight of the water-soluble solvent is added to the reaction mixture.
With respect to the water-soluble solvent, the cooled solvent consisting of 0.06 to 0.09 times by weight of water and the melt-mixed liquid are mixed and crystallized, and the β crystal structure generated by further adding water is stabilized. Tetrakis [3- (3,
A method for crystallization purification of 5-di-tert-butyl-4-hydroxyphenyl) propionyloxymethyl] methane. 2. A water-soluble solvent is added to the reaction mixture in an amount of 0.1-1.
The method according to claim 1, wherein the method is used in a weight ratio. 3. A molten mixture obtained by melt-mixing a reaction mixture containing tetrakis [3- (3,5-ditertiarybutyl-4-hydroxyphenyl) propionyloxymethyl] methane in an aqueous solvent under reflux. The method according to claim 1, wherein the temperature of the used solvent is maintained at reflux. 4. The method according to claim 3, wherein the time for holding the solvent using the molten mixture under reflux is 2 hours or less. 5. The temperature when the cooled solvent and the melt-mixed liquid are mixed is 10 to 50 ° C.
The method described. 6. The method according to claim 1, wherein 0.1 to 0.2 times by weight of water is added to the total water-soluble solvent used.