Crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and production method thereof

Abstract

The present invention addresses the problem of providing an isolate of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane in a form that is suited to industrial production. As a solution, provided are crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane having an onset temperature of an endothermic peak by differential scanning calorimetry is within the range of 226-236° C.

Description

Crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and method for producing the same

[0001] The present invention relates to crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a method for producing the same.

[0002] Tetrakisphenol compounds are useful as raw materials for epoxy resins used in sealing materials, laminate materials, and electrical insulating materials for integrated circuits, curing agents for epoxy resins, color developers and anti-fading agents used in thermal recording, raw materials for electronic materials and photosensitive materials, and are also widely used as additives for antioxidants, disinfectants, antibacterial and antifungal agents, and clathrate compounds. As a method for producing tetrakisphenol compounds, for example, Patent Document 1 specifically describes a method in which a phenol and 2,2-bis(4-oxocyclohexyl)propane (hereinafter sometimes referred to as "4HBPA") are reacted by dehydration condensation in the presence of hydrogen chloride gas using 3-mercaptopropionic acid as a co-catalyst. Meanwhile, Patent Document 1 reports an experimental example of the production of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane (hereinafter sometimes referred to as "Compound A"), a type of tetrakisphenol compound. Patent Document 1 describes that a reaction for synthesizing Compound A was carried out using toluene, t-butylphenol, 4HBPA, dry hydrogen chloride, and octyl mercaptan, followed by washing with saturated saline, dehydration, drying, distilling off the solvent phenol, and recrystallization with ligroin (a mixture mainly composed of saturated hydrocarbons having 7 carbon atoms), yielding a white powder having a melting point of 165 to 169°C.

[0003] Japanese Unexamined Patent Publication No. 49-000250

[0004] When the present inventors produced Compound A according to the production example described in Patent Document 1, the reaction selectivity of Compound A in the synthesis reaction was 45%, as described in Comparative Example 1 below. Although the reaction was carried out for 24 hours, which is longer than the reaction time described in Patent Document 1, the reaction selectivity did not change, and the target compound could not be isolated due to the low reaction selectivity. From these facts, it was revealed that Compound A described in Patent Document 1 could not be said to have been produced with sufficient purity. The present invention has been made against the background of the above-mentioned circumstances, and an object of the present invention is to provide an isolated product of Compound A that is suitable for industrial production and has a sufficiently high purity.

[0005] The present inventors have intensively investigated methods for isolating Compound A and have found that Compound A can be isolated as crystals, thereby completing the present invention.

[0006] The present invention is as follows: 1. A crystal of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane, which exhibits an endothermic peak with an onset temperature in the range of 226 to 236°C in differential scanning calorimetry. 2. The crystal according to 1., which does not exhibit any endothermic peak other than the endothermic peak in the differential scanning calorimetry. 3. The crystal according to 1., which further exhibits an endothermic peak with an onset temperature in the range of 80 to 100°C in the differential scanning calorimetry. 4. A crystal of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane, which exhibits diffraction peaks at diffraction angles 2θ of 8.3±0.2° and 17.2±0.2° in a powder X-ray diffraction peak pattern using Cu-Kα radiation. 5. 6. A crystal of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane, which exhibits diffraction peaks at diffraction angles 2θ of 12.3±0.2°, 14.1±0.2°, and 16.1±0.2° in a powder X-ray diffraction peak pattern using Cu-Kα radiation. 6. A method for producing the crystal according to 1., which comprises a crystallization step of preparing a solution containing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a ketone solvent having 5 to 9 carbon atoms, and precipitating crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane. 7. A method for producing crystals according to 2. or 4., comprising: a crystallization step of preparing a solution containing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a ketone solvent having 5 to 9 carbon atoms, and precipitating crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane; a filtration step of filtering out the crystals precipitated in the crystallization step; and a drying step of drying the crystals filtered out in the filtration step at a temperature in the range of 70 to 150°C.8. A method for producing crystals according to 3. or 5., comprising: a crystallization step of preparing a solution containing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a ketone solvent having 5 to 9 carbon atoms, and precipitating crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane; a filtration step of filtering out the crystals precipitated in the crystallization step; and a drying step of drying the crystals filtered out in the filtration step at a temperature in the range of 15 to 50°C.

[0007] The 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane crystals of the present invention have easy-to-handle properties and are therefore suitable for industrial production, and can be efficiently produced as highly pure 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane. The method for producing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane crystals of the present invention not only enables 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane to be isolated as easily handleable crystals, but also provides an industrially feasible and efficient production process, enabling the production of highly pure 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane.

[0008] Fig. 1 shows a chart of differential scanning calorimetry (DSC) data for the crystals of Compound A obtained in Example 1. Fig. 2 shows a chart of powder X-ray diffraction (PXRD) measurement for the crystals of Compound A obtained in Example 1. Fig. 3 shows a chart of differential scanning calorimetry (DSC) data for the crystals of Compound A obtained in Example 2. Fig. 4 shows a chart of powder X-ray diffraction (PXRD) measurement for the crystals of Compound A obtained in Example 2.

[0009] The present invention will be described in detail below. 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane (compound A) according to the present invention is a compound having the following chemical structure:

[0010] <Reaction Step> There is no limitation on the method for producing Compound A according to the present invention. For example, Compound A can be produced by a reaction step in which 4 equivalents of 2-t-butylphenol and 1 equivalent of 4HBPA (2,2-bis(4-oxocyclohexyl)propane) undergo a dehydration condensation reaction. The amount of 2-t-butylphenol used in the reaction step is preferably 5 to 25 moles per mole of 4HBPA, more preferably 6 to 22 moles, even more preferably 8 to 20 moles, and particularly preferably 8 to 12 moles. If the amount of 2-t-butylphenol used is less than 4 moles, the reaction will be slow, and in addition to the target compound A, a large amount of by-products such as polynuclear compounds in which 4HBPA and 2-t-butylphenol are further condensed will be produced, which is undesirable. Furthermore, if the amount of 2-t-butylphenol used exceeds 30 moles, the reaction rate will improve, but the amount of unreacted 2-t-butylphenol recovered will increase, reducing productivity. Furthermore, crystal precipitation will be slowed, and the amount of compound A produced by the reaction will not reach its saturated solubility in the mixed solution, preventing crystal precipitation, which is undesirable. The reaction temperature for producing Compound A depends on the boiling point of the reaction solvent used, and is preferably in the range of 10 to 80°C, more preferably 10 to 50°C, even more preferably 10 to 25°C, and particularly preferably 15 to 20°C, provided that it does not exceed that range. The reaction pressure for producing Compound A and the temperature for precipitating crystals are typically carried out under normal pressure; however, depending on the boiling point of the organic solvent used, the reaction may be carried out under increased or reduced pressure so that the reaction temperature falls within the above range. Furthermore, when hydrogen chloride gas is used as the acid catalyst, the reaction may be carried out under increased pressure. The method for mixing raw materials and the like in the reaction step is not particularly limited. For example, the entire amount of raw materials and the like to be used may be charged into a reaction vessel at once and mixed, or a mixture containing a solution containing a portion of the 2-t-butylphenol to be used, the acid catalyst, and, if necessary, a co-catalyst and reaction solvent, is mixed with a mixture containing the remaining amounts of 4HBPA and 2-t-butylphenol, and, if necessary, a reaction solvent. The latter mixing method is preferred from the viewpoints of reaction selectivity and the ability to adjust the precipitation rate of the crystals precipitated during the reaction. In this mixing method, it is preferable to carry out the reaction so that the mixing time is within a range of 0.5 to 5 hours and the amounts of raw materials used after mixing are as described above. The reaction time for producing Compound A varies depending on the amount of catalyst and the reaction temperature, but is usually within a range of 1 to 48 hours, and it is preferable for the reaction to be completed within a range of 3 to 24 hours.The end point of the reaction for producing Compound A can be confirmed by liquid chromatography or gas chromatography. The end point of the reaction is preferably the time when unreacted 4HBPA disappears or when an increase in the target compound A is no longer observed.

[0011] (Acid Catalyst) An acid catalyst may be used in the reaction step, and either an inorganic acid or an organic acid catalyst can be used. Examples of inorganic acids include hydrogen chloride gas, hydrochloric acid, sulfuric acid, phosphoric acid, sulfuric anhydride, and the like. Examples of organic acids include aromatic sulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid, alkanesulfonic acids having 1 to 4 carbon atoms such as methanesulfonic acid and ethanesulfonic acid, trifluoromethanesulfonic acid, trichloroacetic acid, and the like. Other examples of acid catalysts that can be used include metal halides such as aluminum chloride and iron chloride, and solid acids such as cation exchange resins. Among these, inorganic acids are preferred. Among inorganic acids, hydrogen chloride gas or hydrochloric acid is more preferred, with hydrogen chloride gas being particularly preferred. The amount of inorganic acid used is preferably in the range of 3 to 18 moles per mole of 4HBPA, more preferably 4 to 15 moles, and particularly preferably 4 to 6 moles.

[0012] (Reaction Solvent) In the reaction step, a reaction solvent need not be used if there are no problems with operability, but may be used to improve operability during industrial production. The reaction solvent used is preferably selected appropriately depending on the solubility of the raw materials used in the reaction step and the product, Compound A. In addition, it is also preferable that the solvent does not distill out of the reaction vessel at the reaction temperature in the reaction to produce Compound A and is inert to the reaction. Examples of solvents that can be used include lower alcohols such as methanol, ethanol, and isopropanol, with methanol being particularly preferred. The amount of the solvent used is in the range of 0.1 to 5.0 times by weight, preferably 0.1 to 3.0 times by weight, more preferably 0.5 to 2.0 times by weight, and even more preferably 0.8 to 1.2 times by weight relative to 4HBPA.

[0013] (Co-catalyst) In the reaction step, a thiol compound may be used as a co-catalyst in combination with the acid catalyst, if necessary. The thiol compound is a compound having a mercapto group, and is not particularly limited as long as it does not adversely affect the reaction selectivity, etc. Examples of such compounds include carboxylic acids having a mercapto group, such as 3-mercaptopropionic acid and thioglycolic acid; alkyl mercaptans having 1 to 12 carbon atoms, such as methyl mercaptan, 1-octanethiol (octyl mercaptan), and 1-dodecanethiol (lauryl mercaptan); and mercaptoalcohols, such as mercaptoethanol and mercaptobutanol. Among these, alkyl mercaptans having 1 to 12 carbon atoms, such as 1-octanethiol, are preferred; methyl mercaptan, 1-octanethiol (octyl mercaptan), and 1-dodecanethiol (lauryl mercaptan) are more preferred; and 1-dodecanethiol (lauryl mercaptan) is particularly preferred. These compounds may be used in the form of an aqueous solution of their sodium salts. The amount of thiol compound used is preferably in the range of 0.01 to 0.50 moles, more preferably 0.05 to 0.15 moles, per mole of 4HBPA. If the amount is less than 0.01 moles, the co-catalyst function cannot be fully exerted, and if the amount exceeds 0.50 moles, the co-catalyst function cannot be exerted any further, and the selectivity does not change much.

[0014] In the reaction step, it is preferable to carry out the reaction under dehydration conditions that can remove water from the reaction system, such as water produced by the reaction and water contained in the acid catalyst used, because the reaction proceeds more quickly, the production of by-products is suppressed, and the target product can be obtained in a higher yield than if dehydration were not carried out. The dehydration method is not particularly limited, and examples thereof include dehydration by adding a dehydrating agent, dehydration under reduced pressure, and dehydration by azeotropy with a solvent under normal pressure or reduced pressure. The dehydrating agent that can be added as needed is not particularly limited, and examples thereof include organic dehydrating agents having an orthoester skeleton such as methyl orthoformate, ethyl orthoformate, methyl orthoacetate, ethyl orthopropionate, methyl ortho-n-butyrate, methyl ortho-i-butyrate, and 1,1,1-trimethoxyoctane; zeolites such as molecular sieve (3A) and molecular sieve (4A); and inorganic anhydrous salts that can contain water of crystallization in the molecule, such as calcium chloride (anhydrous), calcium sulfate (anhydrous), magnesium chloride (anhydrous), magnesium sulfate (anhydrous), potassium carbonate (anhydrous), potassium sulfide (anhydrous), potassium sulfite (anhydrous), sodium sulfate (anhydrous), sodium sulfite (anhydrous), and copper sulfate (anhydrous).

[0015] <Treatment after Completion of Reaction Step> It is preferable to carry out post-treatments on the reaction mixture after the reaction step, such as mixing an aqueous alkali solution such as an aqueous sodium hydroxide solution to neutralize the acid catalyst used in the reaction, removing the separated aqueous layer and, if necessary, washing the oil layer containing the crystals with water, or removing the solvent and 2-t-butylphenol used in excess in the reaction by distillation. Alternatively, Compound A contained in the reaction solution may be dissolved and mixed with an organic solvent that separates from water to obtain a solution of Compound A, followed by a water-washing operation. Compound A can then be isolated by crystallization, separation by column chromatography, or other procedures. The crystals of Compound A of the present invention are produced by carrying out the crystallization step described below using a solution obtained by treating the reaction solution containing Compound A as described above, a solid of Compound A obtained by a conventionally known method, a crystal of Compound A of the present invention, or a mixture of crystalline polymorphs containing the same.

[0016] <Method for Producing Crystals of Compound A of the Present Invention: Crystallization Step> The method for producing crystals of Compound A of the present invention is characterized by comprising a crystallization step of preparing a solution containing Compound A obtained by the method described above and a ketone solvent having a total of 5 to 9 carbon atoms, and precipitating crystals of Compound A. Examples of ketone solvents having 5 to 9 carbon atoms include diethyl ketone, methyl isobutyl ketone, methyl amyl ketone, cyclopentanone, cyclohexanone, cycloheptanone, and cyclooctanone. Among these, methyl isobutyl ketone and cyclohexanone are more preferred, and methyl isobutyl ketone is particularly preferred. The amount of the ketone solvent having a total of 5 to 9 carbon atoms used is in the range of 0.3 to 5.0 times by weight, more preferably 0.5 to 3.0 times by weight, even more preferably 0.5 to 2.0 times by weight, and particularly preferably 0.5 to 1.0 times by weight, relative to the amount of Compound A used. In the crystallization step, it is preferable to mix a chain aliphatic hydrocarbon solvent having 5 to 10 carbon atoms with the prepared solution. Specific examples of the chain aliphatic hydrocarbon solvent having 5 to 10 carbon atoms include pentane, hexane, heptane, octane, and isooctane. Chain aliphatic hydrocarbon solvents having 6 to 8 carbon atoms are preferred, with hexane, heptane, octane, or isooctane being more preferred, heptane or isooctane being even more preferred, and heptane being particularly preferred. The amount of the chain aliphatic hydrocarbon solvent having 5 to 10 carbon atoms used is in the range of 0.5 to 10.0 times by weight relative to the amount of Compound A used, more preferably 1.0 to 7.0 times by weight, even more preferably 2.5 to 7.0 times by weight, and particularly preferably 2.5 to 5.0 times by weight. When precipitating crystals, seed crystals do not need to be used, but it is preferable to use seed crystals. There are no limitations on the crystals used as seed crystals, but the crystals of the present invention obtained without seed crystals at first may be used as seed crystals. The amount of seed crystals used is preferably in the range of 0.1 to 1.0% by weight based on the compound A produced by the reaction. The temperature at which crystals are precipitated from the solution prepared as described above depends on the boiling point of the crystallization solvent used, but is preferably in the range of 60 to 120°C, provided that it does not exceed this boiling point.The crystal precipitation temperature is more preferably in the range of 80 to 120°C, even more preferably in the range of 80 to 110°C, and particularly preferably in the range of 90 to 110°C. After crystal precipitation begins, it is preferable to maintain the same temperature to increase the amount of crystal precipitation. The maintenance time is not particularly limited, but is usually in the range of 1 to 120 hours. After increasing the amount of crystal precipitation, the liquid containing the crystals can be cooled, with the final cooling temperature preferably being 10 to 30°C. The cooling rate during cooling is preferably in the range of 3 to 20°C / hour, more preferably in the range of 5 to 15°C / hour. The precipitated crystals can be isolated by filtration. The isolated crystals are preferably washed with water or an organic solvent. The organic solvent used is preferably a ketone solvent having 5 to 8 carbon atoms or a chain aliphatic hydrocarbon solvent having 5 to 10 carbon atoms, as used in the crystallization step. The amount of the organic solvent used is preferably in the range of 0.5 to 5.0 times by weight, more preferably in the range of 0.5 to 2.5 times by weight, further preferably in the range of 0.5 to 2.0 times by weight, and particularly preferably in the range of 1.0 to 2.0 times by weight, relative to the amount of the crystals of Compound A.

[0017] (Treatment after isolation of crystals) The crystals obtained in the crystallization step are subjected to a drying step under predetermined conditions to remove the solvent adhering to the crystals, and to obtain crystals of Mode 2 and Mode 1, which will be described later. When obtaining crystals of Mode 2, which will be described later, the drying can be carried out at a temperature in the range of 15 to 50°C, preferably in the range of 20 to 50°C, more preferably in the range of 20 to 40°C, and particularly preferably in the range of 20 to 35°C. Drying may be carried out under normal pressure or reduced pressure, but when carried out industrially, a reduced pressure of 10 kPa or less is preferred, a reduced pressure of 5 kPa or less is more preferred, and a reduced pressure of 2 kPa or less is even more preferred, so that the solvent used can be removed. When obtaining crystals of Mode 1, which will be described later, the drying can be carried out at a temperature in the range of 70 to 150°C, preferably in the range of 75 to 130°C, more preferably in the range of 75 to 120°C, and particularly preferably in the range of 80 to 110°C. Drying may be carried out under normal pressure or reduced pressure. When carried out industrially, however, a reduced pressure of 10 kPa or less is preferred, a reduced pressure of 5 kPa or less is more preferred, and a reduced pressure of 2 kPa or less is even more preferred, since this allows the solvent used to be removed.

[0018] <Crystal of Compound A of the Present Invention> The crystal of Compound A of the present invention is characterized by exhibiting an endothermic peak having an onset temperature in the range of 226 to 236°C in differential scanning calorimetry. The onset temperature of the endothermic peak in differential scanning calorimetry of the crystal of the present invention is more preferably in the range of 227 to 235°C, even more preferably in the range of 228 to 234°C, and particularly preferably in the range of 229 to 233°C. The crystal of Compound A of the present invention may be in one of two modes (Mode 1) that exhibits no endothermic peak other than the endothermic peak having an onset temperature in the range of 226 to 236°C in differential scanning calorimetry, and another mode (Mode 2) that further exhibits an endothermic peak having an onset temperature in the range of 80 to 100°C, as described below. The crystal of Mode 1 may also have, and preferably has, the characteristics of Peak Pattern 1 identified by powder X-ray diffraction analysis (PXRD) described below.

[0019] The crystal of the present invention, as set forth in Aspect 2, is characterized in that, in the differential scanning calorimetry analysis, it exhibits an endothermic peak having an onset temperature in the range of 80 to 100°C and an endothermic peak in the range of 226 to 236°C. The onset temperatures of the endothermic peaks further exhibited by the crystal of Aspect 2 in differential scanning calorimetry are more preferably in the range of 82 to 98°C, even more preferably in the range of 84 to 96°C, and particularly preferably in the range of 85 to 95°C. That is, in differential scanning calorimetry analysis, the crystal of Aspect 2 more preferably exhibits an endothermic peak having an onset temperature in the range of 82 to 98°C and an endothermic peak in the range of 227 to 235°C, even more preferably in the range of 84 to 96°C and an endothermic peak in the range of 228 to 234°C, and particularly preferably in the range of 85 to 95°C and an endothermic peak in the range of 229 to 233°C. The crystals of Aspect 2 are crystals of Compound A that include methyl isobutyl ketone, and it is presumed that, in differential scanning calorimetry, elimination of the methyl isobutyl ketone included in the crystals occurs in the range of 80 to 100° C. The crystals of Aspect 2 may also have, and preferably have, the characteristics of Peak Pattern 2 identified by powder X-ray diffraction analysis (PXRD) described below.

[0020] The crystal of Compound A of the present invention is characterized in that, in a powder X-ray diffraction peak pattern using Cu-Kα radiation, it exhibits diffraction peaks at diffraction angles 2θ of 8.3±0.2° and 17.2±0.2° (hereinafter, sometimes referred to as peak pattern 1). In the powder X-ray diffraction peak pattern using Cu-Kα radiation of the present invention, in addition to the above peaks, it is preferable that the diffraction angle 2θ is further 14.6±0.2°, and more preferably, it exhibits diffraction peaks at 12.9±0.2°, 13.7±0.2°, 15.7±0.2°, 16.7±0.2°, and 18.9±0.2°. Note that the peaks in the powder X-ray diffraction using Cu-Kα radiation preferably have a relative intensity of 10 or more, more preferably 25 or more, based on the most intense peak; however, the relative intensity may vary depending on the measurement device and conditions, or in the case of a mixture with other crystals; therefore, the crystalline phase can be identified based on an analysis method of ordinary powder X-ray diffraction analysis. In the powder X-ray diffraction peak pattern of Compound A of the present invention using Cu-Kα radiation, crystals exhibiting Peak Pattern 1 may also have, and preferably have, the characteristics of the endothermic peak of Mode 1 in the above-mentioned differential scanning calorimetry.

[0021] The crystal of Compound A of the present invention is characterized in that, in a powder X-ray diffraction peak pattern using Cu-Kα radiation, it exhibits diffraction peaks at diffraction angles 2θ of 12.3±0.2°, 14.1±0.2°, and 16.1±0.2° (hereinafter, this may be referred to as peak pattern 2). In the powder X-ray diffraction peak pattern using Cu-Kα radiation of the present invention, in addition to the above peaks, it is preferred that the crystal exhibits diffraction peaks at diffraction angles 2θ of 8.7±0.2°, 11.3±0.2°, and 19.9±0.2°, and even more preferred that the crystal exhibits diffraction peaks at 13.6±0.2°, 15.6±0.2°, 16.4±0.2°, and 18.6±0.2°. The peaks in powder X-ray diffraction using Cu-Kα radiation preferably have a relative intensity of 10 or more, more preferably 25 or more, based on the most intense peak. However, the relative intensity may vary depending on the measurement device and conditions, or in the case of a mixture with other crystals. Therefore, the crystalline phase can be identified based on the analytical method of ordinary powder X-ray diffraction analysis. In the powder X-ray diffraction peak pattern using Cu-Kα radiation of Compound A of the present invention, crystals exhibiting peak pattern 2 may also have, and preferably have, the characteristics of the endothermic peak of Aspect 2 in the differential scanning calorimetry analysis described above. It is presumed that such crystals exhibiting peak pattern 2 are crystals of Compound A that include methyl isobutyl ketone.

[0022] The purity of the crystals of Compound A described above is preferably 90.0% or more, more preferably 91.0% or more, and even more preferably 92.0% or more, as a ratio of the peak area of ​​Compound A to the peak areas of all components detected at a wavelength of 280 nm in high performance liquid chromatography (HPLC) analysis. The method for HPLC analysis of the purity of the crystals of the present invention is a method conforming to the HPLC analysis in the analytical methods of the Examples described below. The content of 2-t-butylphenol in the crystals of Compound A of the present invention is preferably 5% by weight or less, more preferably 4% by weight or less, even more preferably 3% by weight or less, and particularly preferably 2% by weight or less. The content of 2-t-butylphenol in the crystals of the present invention can be analyzed by a method conforming to the HPLC analysis in the analytical methods of the Examples described below. Among the crystals of Compound A of the present invention, the crystals of Compound A of the above-described Aspect 1 and the crystals of Compound A showing Peak Pattern 1 have a low content of organic solvent, and are therefore preferred. Specifically, the total content of the ketone solvent having 5 to 9 carbon atoms, which is the organic solvent used in the crystallization step, and the chain aliphatic hydrocarbon solvent having 5 to 10 carbon atoms, which is used as needed, is preferably 5% by weight or less, more preferably 4% by weight or less, even more preferably 3% by weight or less, and particularly preferably 2% by weight or less. The content of 2-t-butylphenol in the crystals of the present invention can be analyzed by a method in accordance with the HPLC analysis method in the analytical methods of the Examples described below.

[0023] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. <Analysis method> 1. High performance liquid chromatography (HPLC) analysis (1) HPLC analysis equipment and conditions (Equipment and conditions) Shimadzu Nexera series LC-40 / manufactured by Shimadzu Corporation Pump: LC-40D Column oven: CTO-40C Detector: SPD-40 Column: HALO C18 column 3.0 × 75 mm Particle size 2.7 μm / manufactured by Advanced Materials Technology Oven temperature: 50°C Flow rate: 0.7 mL / min Mobile phase: (A) 0.2% by volume aqueous acetic acid, (B) methanol Gradient conditions: (B) vol% (time from start of analysis) 50% (0 min) → 80% (4 min) → 100% (18 min) → 100% (30 min) Sample injection volume: 5 μL Detection wavelength: 280 nm, 254 nm (2) Measurement of selectivity of compound A and impurity B in the reaction solution 350 to 450 mg of the reaction solution was collected in a 50 mL volumetric flask and dissolved by mixing with methanol up to the marked line on the volumetric flask. The obtained sample solution was analyzed using the apparatus and conditions described in (1) above, and the composition was calculated based on the area of ​​the detected peak. The selectivity of compound A and impurity B, which will be described later, was calculated using the following formula. (Selectivity) = (peak area ratio of target compound) ÷ {100 - (peak area ratio of 2-tert-butylphenol) - (peak area ratio of solvent)} × 100 (Retention time of each compound) Compound A: 10.4 minutes Impurity B: 12.0 minutes, 14.0 minutes (3) Measurement of Purity of Compound A Crystals 190 to 130 mg of crystals were collected in a 50 mL volumetric flask and dissolved by adding methanol up to the marked line on the volumetric flask. The obtained sample solution was analyzed using the apparatus and conditions described in (1) above, and the purity was calculated based on the area of ​​the detected peak. The area percentage of Compound A in the HPLC analysis was taken as the purity of Compound A. (4) Measurement of Solvent Content of Compound A Crystals (Methyl isobutyl ketone and 2-tert-butylphenol) Several methanol solution samples with different concentrations of the components to be quantified (methyl isobutyl ketone and 2-tert-butylphenol) were prepared and analyzed using the apparatus and conditions described in (1) above.A calibration curve was created from the relationship between the sample concentration of the component to be quantified and the peak area detected by HPLC analysis. 90-130 mg of crystals were placed in a 50 mL volumetric flask and dissolved by adding methanol up to the marked line on the volumetric flask. The resulting sample solution was analyzed using the apparatus and conditions described in (1) above. The amount of solvent contained in the crystals was calculated using the calibration curve.

[0024] 2. Headspace gas chromatography (HS-GC) (1) HS-GC analysis equipment and conditions Gas chromatography Equipment: GC-2010 Plus / Shimadzu Corporation Column: InertCap-1 60 m × 0.25 mm Φ / GL Sciences Inc. Film thickness: 0.25 μm Detector: FID Vaporization chamber temperature: 300 ° C. Detector temperature: 310 ° C. Column temperature: 40 ° C. Column heating conditions (retention time): 40 ° C. (10 min) → 20 ° C. / min → 300 ° C. (5 min) Makeup gas (nitrogen) flow rate: 30.0 mL / min Hydrogen flow rate: 40.0 mL / min Air flow rate: 400.0 mL / min Carrier gas: Nitrogen Pressure: 118 kPa Column flow rate: 0.92 mL / min Linear velocity: 19.9 cm / sec Total flow rate: 8.5 mL / min Split ratio: 5 HS sampler Apparatus: TurboMatrix HS40 / PerkinElmer Co., Ltd. HS carrier gas pressure: 154.0 kPa Oven temperature: 100 ° C. Needle temperature: 105 ° C. Transfer temperature: 105 ° C. Incubation time: 20 minutes Pressurization time: 3 minutes Withdrawal time: 0.5 minutes Injection time: 0.05 minutes (2) Measurement of solvent content in crystals of Compound A (n-heptane) For the component to be quantified (n-heptane), multiple NMP solution samples with different concentrations were prepared and analyzed using the apparatus and conditions described in (1) above. A calibration curve was created from the relationship between the sample concentration of the component to be quantified and the peak area detected by HS-GC analysis. 0.15 g of the crystals was dissolved in 9.85 g of N-methylpyrrolidone, and 2.90 g of the resulting sample solution was analyzed using the apparatus and conditions described in (1) above. The amount of solvent contained in the crystals was calculated using the calibration curve.

[0025] 3. Differential Scanning Calorimetry (DSC) (Analysis Method) 2-3 mg of crystals were placed in an aluminum sample container, a lid was attached, and the container was pressed to create a sample. The resulting sample was analyzed using the following equipment and conditions. (Equipment and Conditions) Equipment: DSC7020 / Hitachi High-Tech Science Corporation Heating rate: 10°C / min. Measurement temperature range: 30-300°C. Measurement atmosphere: Nitrogen 50 mL / min.

[0026] 4. Powder X-ray diffraction (PXRD) analysis The crystals were thoroughly ground in a mortar and filled into a measurement cell. The obtained sample was analyzed using the following equipment and conditions. (Measurement conditions) Equipment: MiniFlex 600-C / Rigaku Corporation X-ray source: CuKα Scan axis: 2θ / θ Mode: Continuous Measurement range: 2θ = 5° to 90° Step: 0.02° Speed ​​measurement time: 10° / min. Entrance slit: 0.25° Receiving slit: 13.00 mm Tube voltage: 40 kV Tube current: 15 mA

[0027] Comparative Example 1 A 1 L four-neck flask equipped with a thermometer, a stirrer, and a condenser was charged with 2-tert-butylphenol (152.0 g), 2,2-bis(4-oxocyclohexyl)propane (30.0 g), and toluene (82.0 g), and the atmosphere in the flask was replaced with nitrogen. Next, n-octyl mercaptan (1.4 g) was charged, and hydrochloric acid gas was blown in over 1 hour and 30 minutes at a liquid temperature of 26 to 27°C, followed by stirring for 24 hours and 25 minutes at a liquid temperature of 25 to 26°C. The selectivity for Compound A was 45% 3 hours after completion of the hydrochloric acid gas blowing, and 46% at the end of post-stirring. Furthermore, in order to identify the main impurities contained in the reaction solution, LC-MS (ESI) analysis was performed under the above HPLC analysis conditions. A component with a molecular weight of 649.5 (deprotonated molecule) was detected among the components with retention times of 12.0 minutes and 14.0 minutes in the above HPLC analysis. This component has a molecular weight equivalent to a compound having a molecular structure or partial structure such as that shown in the following formula (B), which is presumed to be produced as an intermediate in the synthesis of Compound A by the reaction of 2-tert-butylphenol and 2,2-bis(4-oxocyclohexyl)propane, and it is presumed that the reaction solution contains such a compound (hereinafter referred to as Impurity B). The total selectivity of this Impurity B at the end of post-stirring was 25%.

[0028] Example 1 A 1 L four-neck flask equipped with a thermometer, stirrer, and condenser was charged with 2-tert-butylphenol (155.3 g), and the atmosphere inside the flask was replaced with nitrogen. Next, n-dodecyl mercaptan (3.5 g) and methanol (15.5 g) were charged, and hydrochloric acid gas was blown into the flask over 1.25 hours at a liquid temperature of 17 to 27°C. Meanwhile, a dropping solution was prepared by mixing 2,2-bis(4-oxocyclohexyl)propane (35.6 g), 2-tert-butylphenol (76.8 g), and methanol (17.7 g). The resulting dropping solution was added over 2 hours while maintaining the liquid temperature in the flask at 15 to 19°C, and the mixture was further stirred for 50 minutes at a liquid temperature of 17 to 19°C. The selectivity of compound A in the reaction solution at the end of stirring was 86%. The total impurity B content was 5.8%. The reaction solution was neutralized using 75% phosphoric acid (0.9 g), 16% aqueous sodium hydroxide solution (206.2 g), and concentrated hydrochloric acid (1.5 g), and toluene (155.4 g) was added. The solution was heated to 65 ° C., and the aqueous layer (247.4 g) was removed from the two-layer solution. The oil layer was then washed three times with water (100 g) at a liquid temperature of 66 ° C. to 73 ° C. The resulting oil layer was distilled at an internal pressure of 1.2 kPa and a liquid temperature of 166 ° C., and 291.8 g of a liquid containing toluene and excess 2-tert-butylphenol was distilled out. After adding methyl isobutyl ketone (60.5 g) to the distilled oil, n-heptane (302.0 g) was added dropwise at an internal temperature of 98 to 103 ° C. over 3.25 hours. After the dropwise addition was completed, the mixture was cooled to 75 ° C. at a cooling rate of 10 ° C. / Hr, and then the heating equipment was turned off and the mixture was cooled to 25 ° C. 17.5 hours after the start of cooling, a mixed solvent of methyl isobutyl ketone and n-heptane (methyl isobutyl ketone: n-heptane = 1:5 (weight ratio)) (179.9 g) was added all at once, and the mixture was stirred at an internal temperature of 25 ° C. for 3 hours. The precipitated crystals were separated by centrifugation and washed with n-heptane (127.6 g). In addition, the crystals remaining in the flask were washed with a mixed solvent of methyl isobutyl ketone and n-heptane (methyl isobutyl ketone: n-heptane = 1:5) (71.5 g), and these were also separated by filtration. By the above operation, crystals containing the solvent (286.6 g) were obtained.Of the solvent-containing crystals (286.6 g) obtained by filtration, 4.3 g was dried at 30°C for 2 hours using an evaporator under a reduced pressure of 0.6 kPa internal pressure. This procedure yielded 2.0 g of crystals. The purity of the obtained Compound A crystals was 92 area % by HPLC analysis. The crystals also contained 2-tert-butylphenol (1.5 wt%), methyl isobutyl ketone (19.3 wt%), and n-heptane (0.1 wt%). DSC and PXRD analyses of the obtained crystals were performed using the methods described above. The analytical charts are shown in Figures 1 and 2, respectively. In the DSC analysis, endothermic peaks were observed at 92°C and 230°C (peak onset temperatures). The endothermic peak at 92°C is thought to correspond to the desorption of the solvent contained in the crystals, and the endothermic peak at 230°C is thought to correspond to the melting of the crystals. A diffraction pattern was also observed in the PXRD analysis, confirming the existence of crystals. Table 1 shows the diffraction angles 2θ (°) of the diffraction peaks that appeared and peaks with a relative intensity of 25 or more based on the peak with the greatest intensity.

[0029]

[0030] Example 2 Of the solvent-containing crystals (286.6 g) obtained by filtration in Example 1, 281.2 g was heated at 28°C for 1.25 hours, then from 28°C to 74°C over 1.25 hours, while maintaining a reduced pressure of 2.2 kPa using an evaporator, and finally dried at 74 to 80°C for 5 hours. Through these operations, crystals (103.8 g, yield 88 mol% (based on the amount of 2,2-bis(4-oxocyclohexyl)propane) were obtained. HPLC analysis revealed that the purity of the obtained crystals of Compound A was 93 area %. The crystals also contained 2-tert-butylphenol (1.3 wt%) and methyl isobutyl ketone (0.9 wt%). The n-heptane contained in the crystals obtained in Example 1 was not detected. DSC and PXRD analyses of the obtained crystals were performed using the methods described above. The analytical charts are shown in Figures 3 and 4, respectively. In DSC analysis, an endothermic peak (peak onset temperature: 231°C) corresponding to the melting of the crystal was clearly observed. A diffraction pattern was also observed in PXRD analysis, confirming that the product was crystalline. The diffraction angles 2θ (°) of the diffraction peaks that appeared and peaks with a relative intensity of 25 or more based on the most intense peak are shown in Table 2.

[0031]

[0032] In Comparative Example 1, in which Compound A was produced according to the production example described in Patent Document 1, the reaction selectivity of Compound A in the synthesis reaction was 45%. Furthermore, the reaction was carried out for 24 hours, exceeding the reaction time described in Patent Document 1, but the reaction selectivity did not change. The total selectivity of impurity B, presumed to be a synthetic intermediate of Compound A, was 25%. Therefore, due to the low reaction selectivity of Compound A, Compound A could not be isolated. Patent Document 1 describes the production of a white powder of Compound A having a melting point of 165-169°C, but these facts make it clear that Compound A was not produced with sufficient purity. Meanwhile, in Examples 1 and 2 according to the present invention, novel crystals of Compound A were discovered that were sufficiently pure, easy to handle, and completely different in characteristics from previously known crystals. The crystals of the embodiment obtained in Example 1 are highly useful because they can be obtained in the embodiment obtained in Example 2, which contains a low amount of methyl isobutyl ketone, while maintaining the crystal shape, without melting the enclosed organic solvent, methyl isobutyl ketone. The crystals of the embodiment obtained in Example 2 are more useful because they contain a small amount of organic solvent, which can reduce the amount of solvent exposure during storage and transportation of Compound A and during the production of resins and derivatives using the same, thereby contributing to the health of workers handling the compound and the protection of the environment.

Claims

1. Crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane, which show an endothermic peak with an onset temperature in the range of 226 to 236°C in differential scanning calorimetry.

2. The crystal according to claim 1, which does not exhibit any endothermic peak other than the endothermic peak in the differential scanning calorimetry analysis.

3. The crystal according to claim 1, which further exhibits an endothermic peak with an onset temperature in the range of 80 to 100°C in the differential scanning calorimetry analysis.

4. Crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane, which exhibit diffraction peaks at diffraction angles 2θ of 8.3±0.2° and 17.2±0.2° in a powder X-ray diffraction peak pattern using Cu-Kα radiation.

5. A crystal of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane, which exhibits diffraction peaks at diffraction angles 2θ of 12.3±0.2°, 14.1±0.2°, and 16.1±0.2° in a powder X-ray diffraction peak pattern using Cu-Kα radiation.

6. A method for producing the crystals according to claim 1, comprising a crystallization step of preparing a solution containing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a ketone solvent having 5 to 9 carbon atoms, and precipitating crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane.

7. A method for producing crystals according to claim 2 or 4, comprising a crystallization step of preparing a solution containing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a ketone solvent having 5 to 9 carbon atoms, and precipitating crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane; a filtration step of filtering out the crystals precipitated in the crystallization step; and a drying step of drying the crystals filtered out in the filtration step at a temperature in the range of 70 to 150°C.

8. A method for producing crystals according to claim 3 or 5, comprising a crystallization step of preparing a solution containing 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane and a ketone solvent having 5 to 9 carbon atoms, and precipitating crystals of 2,2-bis(4,4-bis(3-t-butyl-4-hydroxyphenyl)cyclohexyl)propane; a filtration step of filtering out the crystals precipitated in the crystallization step; and a drying step of drying the crystals filtered out in the filtration step at a temperature in the range of 15 to 50°C.

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