JPWO2015002146A1 - Crystal of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane and method for producing the same - Google Patents

Abstract

It is an object of the present invention to provide a novel crystal of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane and a method for producing the same. The solution includes 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane crystal and 1,1-bis (4- (2-hydroxyethoxy) phenyl). A non-crystal of −3,3,5-trimethylcyclohexane is dissolved in at least one solvent selected from methanol or methyl ethyl ketone, and then crystallized from the solution at a temperature not higher than 0 ° C. and not lower than the melting point of the solvent. Is a method for producing 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane crystal.

Description

  The present invention relates to a novel crystal of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane and a method for producing the same.

1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane (hereinafter sometimes referred to as BPTMC-2EO) is known to be a useful compound for polyester. ing. (Patent Document 1, Non-Patent Document 1)
Such BPTMC-2EO is conventionally known to be obtained by reacting 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane with ethylene oxide or ethylene carbonate. In the obtained BPTMC-2EO, no crystal was obtained, such as no melting endothermic peak was confirmed by differential scanning calorimetry.
Thus, although the amorphous body of BPTMC-2EO is known, the crystalline body is not known, and in addition, it was not easy to obtain BPTMC-2EO as a crystalline body.

And since the conventional amorphous BPTMC-2EO is solidified at room temperature, when using the one stored in a container or the like, it must be raised to a liquid state again, or the solidification temperature. It was necessary to maintain the above temperature.
Also, even if cut into a certain size or processed into a granular or flaky shape, they may stick together during storage and become a lump or adhere to the container, making it difficult to remove from the container. Although this lump is not completely attached, the handling is very poor, and it becomes inefficient when used in large quantities industrially. For example, if the non-crystalline BPTMC-2EO is pulverized and stored, it becomes a lump, so that it is necessary to scrape or pulverize again when taking it out of a container or the like, which is troublesome.
Furthermore, in order to obtain a high-quality resin such as polyester or polycarbonate, it is necessary to use a stable and high-purity BPTMC-2EO with few impurities as a raw material, but this amorphous BPTMC-2EO is a column. The purity can be increased only by an industrially inefficient method such as separation, and it can only be obtained as a low-purity one.

German Open No. 4138245

Macromolecules, 44, 4049-4056 (2011)

  In view of the above-mentioned background art, the present invention provides a novel crystalline body of stable high-purity BPTMC-2EO that is easy to store and handle, and a method for producing the crystalline body by an industrially easy method. The task is to do.

The present invention for solving the above problems is as follows.
1. Crystals of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane.
2. 2. The crystal body according to 1, wherein the endothermic peak top temperature by differential scanning calorimetry is in the range of 75 to 100 ° C.
3. After dissolving an amorphous form of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane in at least one solvent selected from methanol or methyl ethyl ketone, The solution is characterized by crystallizing dissolved 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane at a temperature not higher than 0 ° C. and not lower than the solvent melting point. A method for producing a crystal of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane.
4. The amorphous form of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane is 1,1-bis (4-hydroxyphenyl) -3,3,5. -1,1-bis (4- (2-hydroxyethoxy) phenyl) -3 according to 3, which is obtained by reacting trimethylcyclohexane with ethylene carbonate or ethylene oxide in the presence of a catalyst. A method for producing a crystal of 3,5-trimethylcyclohexane.

The BPTMC-2EO crystals obtained according to the present invention do not stick together and form a lump even when stored for a long period of time, and have very little adhesion to the container. Moreover, when taking out from the preserve | save container etc., fluidity | liquidity is good, and preservability and workability | operativity are favorable.
Furthermore, a high purity product of BPTMC-2EO can be efficiently obtained by the method for producing a crystal according to the present invention.

DSC measurement result of Example 1 DSC measurement result of Example 2 DSC measurement result of Example 3 Powder X-ray diffraction analysis measurement result of Reference Example 1 DSC measurement result of crystal obtained by further drying in Example 2 Results of powder X-ray diffraction analysis of Example 3

A method for obtaining a non-crystal of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane, which is a raw material used for obtaining the crystal of the present invention, will be described.
Although there is no restriction | limiting in particular about the method of obtaining the amorphous | non-crystalline substance, Conventionally, 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane is 1,1-bis. It is known to be obtained by reacting (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane with ethylene oxide or ethylene carbonate in the presence of a catalyst, and this method can be employed.

  However, this method using ethylene oxide requires a pressure reactor such as an autoclave at the time of synthesis because ethylene oxide is a gas at room temperature. Further, ethylene oxide has toxicity, flammability, explosiveness, etc. There is a problem that is difficult.

On the other hand, the method using ethylene carbonate is 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5 because ethylene carbonate has low toxicity, odorlessness, and low flammability. -It is easy to industrially produce trimethylcyclohexane.
Therefore, a preferable method for obtaining an amorphous body of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane, which is a raw material for obtaining the crystalline body of the present invention, In this method, 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane and ethylene carbonate are reacted in the presence of a catalyst.

There is no restriction | limiting in particular about this reaction, Although a well-known method can be used, For example, 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane is potassium hydroxide, for example. 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane is obtained by reaction with ethylene carbonate in the presence of a catalyst such as. In this reaction, the raw material molar ratio of 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane to ethylene carbonate is 1,1-bis (4-hydroxyphenyl) -3,3,5- Trimethylcyclohexane / ethylene carbonate: in the range of about 1/2 to 1/5, preferably in the range of about 1/2 to 1/3.
Here, in addition to the above potassium hydroxide, generally known catalysts can be used as the catalyst, and quaternary ammonium salts such as tetraethylammonium bromide and tetramethylammonium chloride, potassium iodide, sodium bromide and the like. Alkali metal halides, triorganophosphine compounds such as triphenylphosphine and tributylphosphine, amine catalysts such as 1-methylimidazole, potassium carbonate, calcium carbonate, magnesium carbonate, magnesium hydroxide, calcium hydroxide, sodium hydroxide, Examples of the alkali catalyst include sodium bicarbonate, sodium methoxy, and phenoxy sodium. These catalysts may be used alone or in combination of two or more.
The amount of the catalyst used is 0.001 to 10% by weight, preferably 0.01 to 1% by weight of 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane used. is there.

It is also possible to carry out the reaction without solvent by using an excessive amount of ethylene carbonate. However, it is usually carried out using an organic solvent from the viewpoint of economy and operability.
When a reaction solvent is used, various known solvents that are inert to the reaction can be used. Examples of the reaction solvent include aromatic hydrocarbons such as toluene and xylene, ether solvents such as tetrahydrofuran, dioxane, and 1,2-dimethoxyethane, ketone solvents such as acetone and methyl isobutyl ketone, chloroform, and 1,2. -Halogenated hydrocarbons such as dichloroethane, aliphatic alcohols such as butanol and ethylene glycol, and polar solvents such as dimethylformamide and dimethyl sulfoxide.
Although there is no restriction | limiting in particular regarding the usage-amount of a reaction solvent, when too much usage-amount is unpreferable in terms of production efficiency etc., 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane Preferably it is the range of 50-300 weight part with respect to 100 weight part, More preferably, it is the range of 100-200 weight part.

The reaction may be performed in an air atmosphere or an inert gas atmosphere, but in order to suppress coloring of the reaction product, an inert gas atmosphere such as nitrogen or argon is preferable.
The reaction temperature is not particularly limited as long as the reaction proceeds. Usually, the reaction is performed under heating. For example, it is carried out at 100 ° C. to 250 ° C., preferably under reflux of the solvent.
The reaction time depends on the reaction temperature, the amount of ethylene carbonate to be used, the amount and type of the catalyst, etc., but is usually about 5 to 24 hours. In the reaction, the point at which the generation of carbon dioxide gas has stopped can be used as a measure for the completion of the reaction.
After completion of the reaction, an amorphous form of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane can be obtained by separation and purification according to a conventional method. .

Examples of the treatment for separation / purification include hydrolysis of excess ethylene carbonate remaining in the reaction system after completion of the reaction by adding water under heating, and when an alkali catalyst is used, this contains an acid. Neutralize by adding water (for example, hydrochloric acid, sulfuric acid), acetic acid, propionic acid and the like. Then, if necessary, after adding a solvent that separates from water, the oil layer is washed with water several times, and the low-boiling substances such as solvent are distilled off under reduced pressure from the oil layer obtained by separating and removing the aqueous layer. Or a method of drying.
The crude purified product of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane as the raw material according to the present invention thus obtained is endothermic by differential scanning calorimetry. It is an amorphous material having no peak, and is a resinous solid at room temperature.
The purity of the amorphous BPTMC-2EO is usually 90% or more, preferably 95% or more, and more preferably 97% or more.

Surprisingly, the non-crystalline substance of BPTMC-2EO is heated and dissolved by adding only a specific organic solvent, that is, methanol or methyl ethyl ketone, and the specific temperature is 0 ° C. or less. In addition, it has been found that crystals can be precipitated by maintaining the temperature at a temperature equal to or higher than the melting point of the solvent, and can be taken out as a crystal as a result.
The amount of methanol or methyl ethyl ketone used is 2 to 10 parts by weight, preferably 2.5 to 6 parts by weight, based on 1 part by weight of the non-crystalline BPTMC-2EO (however, the low-purity one is 100% in terms of purity). Parts, more preferably 3 to 5 parts by weight.
Although there is no restriction | limiting in particular about the melt | dissolution method of BPTMC-2EO, For example, it heats and melt | dissolves at about 40 to 60 degreeC under stirring. Thereafter, crystals are precipitated from the solution by keeping the temperature at 0 ° C. or lower and the temperature not lower than the solvent melting point. The crystallization temperature is preferably in the range of -20 ° C to 0 ° C, more preferably -20 ° C to -5 ° C.
The crystallization method is not particularly limited. For example, the crystal is precipitated by cooling to a temperature of about −10 ° C. with stirring, and then the temperature is maintained or further cooled to increase the crystal. In the cooling step before crystal precipitation, when the solution is in a supercooled state or the solubility is in a saturated state or a state close thereto, an appropriate amount of seed crystals may be added to promote smooth crystal precipitation. In addition, by using the seed crystal in this way, a higher-purity crystal may be obtained. (In the case of using seed crystals, a crystallization filtration step without seed crystals is required at least once before that.)
In addition, a poor solvent such as toluene may be added for the purpose of improving the yield after crystal precipitation within a range not inhibiting the effect.
Subsequently, the crystals thus precipitated are filtered off and dried to obtain a high-purity crystal of BPTMC-2EO according to the present invention.

The crystal of BPTMC-2EO according to the present invention obtained by this method has an endothermic peak top temperature in the range of 75 to 100 ° C. in differential scanning calorimetry. The endothermic peak top temperature is preferably in the range of 80 to 95 ° C, more preferably in the range of 85 to 92 ° C, and particularly preferably in the range of 86 to 90 ° C.

In the differential scanning calorimetry, the crystal according to the present invention may have an endothermic peak in addition to the endothermic peak having an endothermic peak top temperature in the range of 75 to 100 ° C. For example, depending on the crystallization conditions, an adduct crystal composed of an adduct of a solvent and BPTMC-2EO may be generated. In such a case, in addition to the range of 75 to 100 ° C., other endothermic peaks are also present. Exists. In the case of a crystal having an endothermic peak other than an endothermic peak having an endothermic peak top temperature in the range of 75 to 100 ° C., an endothermic peak area having an endothermic peak top temperature in the range of 75 to 100 ° C. Crystals larger than the peak area are preferred.
The purity of such BPTMC-2EO crystal according to the present invention is usually 95 to 100%, preferably 97 to 100%, particularly preferably 98 to 100%. Crystals used in the production of the crystal according to the present invention When seed crystals are not used in the deposition solvent, methyl ethyl ketone tends to produce adduct crystals composed of adducts with BPMC-2EO.

Differential scanning calorimetry (DSC) measurement conditions-Differential scanning calorimeter: Shimadzu differential scanning calorimeter (model number: DSC-60)
・ Measurement sample amount: 2-3mg
・ Temperature increase rate: 10 ° C./min (30 ° C. to 200 ° C.)
・ Nitrogen flow rate: 50 ml / min <Powder X-ray diffraction analysis> Measurement conditions Powder X-ray diffractometer: Rigaku SmartLab
X-ray: CuKα ray tube voltage and tube current: 45kV, 200mA
Scan speed: 20.0000 deg / min

Reference Example 1 (Synthesis example of BPTMC-2EO)
In a four-necked flask equipped with a stirring blade, a thermometer, and a reflux condenser, 1086.5 g of 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane, granular potassium hydroxide 11 having a purity of 85% 11 .6 g, ethylene carbonate (678.1 g) and toluene (1629.8 g) were charged, and the atmosphere in the flask was replaced with nitrogen, followed by heating to 114 ° C. with stirring. Thereafter, the reaction was continued at 109 ° C. to 113 ° C. with stirring for 14 hours. Carbon dioxide evolution continued during the reaction.
After completion of the reaction, 25.2 g of water was added and hydrolysis was performed at 110 ° C. for 1 hour. The refluxed water was distilled out of the system. The mixture was further cooled to 80 ° C. and neutralized by adding 90% acetic acid.
To the solution, 1267 g of toluene and 700 g of water were added and stirred, and then allowed to stand to separate and remove the aqueous layer. 700 g of water was added to the obtained oil layer, and the mixture was allowed to stand after stirring, and a water washing operation for separating and removing the aqueous layer was performed twice. The obtained oil layer was heated to 133 ° C. under normal pressure and concentrated to remove low-boiling substances such as a solvent. Further, the concentration was continued under reduced pressure to the conditions of 0.6 kPa and 140 ° C.
After concentration, the obtained residual liquid was 1368 g of a pale yellow liquid and was BPTMC-2EO having a purity of 95.0% as measured by a high performance liquid chromatography method (HPLC method).
When left at room temperature, the liquid solidified and became a resinous material.
Powder obtained by finely grinding the obtained resinous material was analyzed by powder X-ray diffraction. The measurement results are shown in FIG.
In the powder X-ray diffraction analysis, it was found that there was no sharp peak characteristic of the crystalline form, a broad halo pattern at a diffraction angle (2θ) of 5 ° to 30 °, and an amorphous form.

Example 1 (crystallization with methanol solvent)
After adding 8.0 g of methanol to 2.0 g of resinous BPTMC-2EO having a purity of 95.0% obtained in Reference Example 1, the mixture was cooled to −10 ° C. and left at the same temperature for another 24 hours. . The precipitated crystals were separated by filtration while maintaining at -10 ° C, and the obtained crystals were dried to obtain 1.6 g of white crystals.
The purity of the obtained crystal was 97.2% (HPLC method), the melting endothermic range by DSC was 76 to 92 ° C, and the endothermic maximum (peak top) was 86 ° C.
The DSC measurement result is shown in FIG.

Example 2 (crystallization with methyl ethyl ketone)
After adding 8.0 g of methyl ethyl ketone to 2.0 g of the resinous BPTMC-2EO obtained in Reference Example 1 and dissolving it, the mixture was cooled to −10 ° C. and allowed to stand at the same temperature for 24 hours. Crystals precipitated while being kept at −10 ° C. were filtered off and dried at room temperature under reduced pressure for 2 hours to obtain 0.61 g of white crystals.
The purity of the obtained crystals is 97.9% (HPLC method), and the measurement results by DSC have endothermic ranges at 53 to 62 ° C. (peak top 57 ° C.) and 77 to 92 ° C. (peak top 86 ° C.). Of these, the maximum melting endotherm was 86 ° C.
The DSC measurement result is shown in FIG.
The crystals obtained by further drying the obtained crystals were subjected to DSC measurement. The endothermic melting range as determined by DSC measurement was 78 to 93 ° C, and the maximum endotherm (peak top) was 87 ° C.
The DSC measurement result is shown in FIG.

Example 3
In a four-necked flask equipped with a stirring blade, a thermometer, and a reflux condenser, 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane 93.0 g, ethylene carbonate 58.1 g, purity 85% Were charged with 0.99 g of granular potassium hydroxide, 0.97 g of tetrabutylammonium bromide, and 140 g of toluene. After the atmosphere in the flask was replaced with nitrogen, the temperature was raised to 109 ° C. with stirring. Thereafter, the reaction was continued at 109 ° C. to 114 ° C. for 10 hours with stirring.
1.1 g of water was added to the reaction completion solution, and hydrolysis was performed at 110 ° C. for 1 hour. The mixture was further cooled to 80 ° C. and neutralized by adding acetic acid.
140 g of toluene and 50 g of water were added to the solution, and the mixture was stirred at 70 ° C. for 1 hour, and then allowed to stand to separate and remove the aqueous layer. 50 g of water was added to the obtained oil layer, and the mixture was stirred at 70 ° C. for 1 hour and then allowed to stand, and a water washing operation for separating and removing the aqueous layer was performed twice.
The resulting oil layer was concentrated to remove low-boiling substances such as solvents. Concentration was continued up to 2.0 kPa and 130 ° C. (residual liquid temperature).

114.9 g of the obtained residual liquid was BPTMC-2EO having a purity of 95.6% (HPLC method). 80 g of methanol was added to 20 g of the residual liquid, and the mixture was heated to 60 ° C. and dissolved. The solution was cooled to −10 ° C. with stirring, and the stirring was continued at this temperature for 24 hours. The precipitated crystals were separated by filtration and dried to obtain 13.4 g of crystals having a purity of 97.9% (HPLC method). Obtained. 54 g of methanol was added to the crystals, and the mixture was heated to 60 ° C. and dissolved. The solution was cooled to −10 ° C. with stirring, and the stirring was continued at this temperature for 24 hours. Then, the precipitated crystals were separated by filtration and dried to obtain 9.7 g of crystals having a purity of 98.8% (HPLC method). Obtained. 39 g of methanol was further added to the crystals, and the mixture was heated to 60 ° C. and dissolved. The solution was cooled to −10 ° C. with stirring, and the stirring was continued at this temperature for 24 hours. The precipitated crystals were separated by filtration and dried to obtain 6.7 g of white crystals having a purity of 99.1% (HPLC method). Obtained.
When this crystal was subjected to DSC measurement, there was an endothermic peak at 70 to 95 ° C., and the endothermic maximum (peak top) was 88.4 ° C. The DSC measurement result is shown in FIG. 3, and the powder X-ray diffraction analysis result is shown in FIG.

Comparative Example 1 (Methanol solvent / high temperature)
Although it carried out like Example 1 except having made cooling temperature 2 ° C, precipitation of a crystal was not able to be checked.

Comparative Example 2 (Methyl ethyl ketone solvent / high temperature)
Although it carried out like Example 2 except having made cooling temperature 2 ° C, precipitation of a crystal was not able to be checked.

Comparative Example 3 (Toluene solvent)
Although it carried out like Example 1 except having used toluene as a solvent and leaving it to stand at room temperature (25-30 ° C), a crystal did not precipitate. Moreover, although it carried out like the above except having made cooling temperature 2 degreeC, the crystal | crystallization did not precipitate.
Further, except that the cooling temperature was −10 ° C., it was carried out in the same manner as described above. However, crystals were not precipitated just by forming a separation layer.

Comparative Example 4 (ethanol solvent)
Although it carried out similarly to the comparative example 3 except having used ethanol for the solvent, the crystal | crystallization did not precipitate in all.

Comparative Example 5 (methyl isobutyl ketone solvent)
Although it carried out similarly to the comparative example 3 except having used methyl isobutyl ketone for the solvent, neither crystal | crystallization precipitated.

Comparative Example 6 (heptane solvent)
Except that heptane was used as a solvent, the same procedure as in Comparative Example 3 was performed, but in any case, a separation layer was formed and no crystals were precipitated.

(Confirmation of storage and handling)
The amorphous body (resinous BPTMC-2EO) obtained in Reference Example 1 was finely pulverized. 1.0 g of the pulverized non-crystalline substance and 1.0 g of the 99.1% pure crystalline substance obtained in Example 3 were placed in a 20 ml glass sample bottle, capped, and 24 g. Left for hours.
Thereafter, the lid was opened and the sample bottle was turned upside down to confirm the fluidity. Although 1.0 g of the crystal body of Example 3 all came out of the sample bottle, the non-crystal body obtained in Reference Example 1 adhered to the wall surface of the sample bottle and further adhered to each other to form a lump. I didn't get out of it at all, and when I hit the bottom of the bottle, it didn't fall at all.
Furthermore, the purity obtained in Example 2 was 97.9%, and the endothermic range by DSC was 53 to 62 ° C. (peak top 57 ° C.) and 77 to 92 ° C. (peak top 86 ° C.). The fluidity was confirmed in the same manner as described above except that powder was used. In the same manner as the crystal body of Example 3, all the 0.5 g of the crystal body of Example 2 came out of the sample bottle.
According to this result, the crystalline material of the present invention does not lose fluidity even when stored as a powder, and is superior in handling property when taken out from a bottle and handled than the amorphous material according to Reference Example 1.

Claims (4)

  Crystalline of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane.   The endothermic peak top temperature according to differential scanning calorimetry is in the range of 75 to 100 ° C.   An amorphous form of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane is dissolved in at least one solvent selected from methanol or methyl ethyl ketone, and then the solution is used. Crystallized dissolved 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane at a temperature of 0 ° C. or lower and a solvent melting point or higher, A method for producing a crystal of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane.   The amorphous form of 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3,3,5-trimethylcyclohexane is 1,1-bis (4-hydroxyphenyl) -3,3,5-trimethyl. The 1,1-bis (4- (2-hydroxyethoxy) phenyl) -3, 3, which is obtained by reacting cyclohexane with ethylene carbonate or ethylene oxide in the presence of a catalyst. A method for producing a crystal of 3,5-trimethylcyclohexane.