JP4438465B2 - Method for producing tetrakis (4-hydroxyphenyl) ethane compound - Google Patents

Description

  The present invention relates to a method for producing a high-purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound with high yield and high efficiency by reacting phenols with glyoxal or a glyoxal derivative. About.

  1,1,2,2-tetrakis (4-hydroxyphenyl) ethane and its analogs (hereinafter referred to as “1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound”) are heat-resistant epoxy resins It is a useful compound as a raw material for production, a curing agent for epoxy resins, a ballast agent for photoresists related to photoresists, a cresol novolac resin modifier, an antioxidant and the like. In recent years, it has attracted attention as a host compound of an inclusion compound, and many studies have been made (Patent Documents 1 to 3).

Conventionally, as a method for producing a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound, for example,
(A) a method in which a phenol and glyoxal or a glyoxal derivative are subjected to a condensation reaction in a state where the water content of the reaction system is maintained at 2% by weight or less (Patent Document 4),
(B) A method of condensing phenols with glyoxal or a glyoxal derivative in the presence of a mixed acid catalyst of sulfuric acid and phosphoric acid in a solvent-free or water or organic solvent at a low temperature of −10 to 10 ° C. 5),
(C) A method of condensing phenols and glyoxal or a glyoxal derivative in the presence of an acidic catalyst, then distilling off volatile components and treating the residue with a specific solvent (Patent Document 6),
(D) A method of reacting a phenol with glyoxal or a glyoxal derivative at a specific temperature in the presence of a specific amount of acetone is known (Patent Document 7).

  However, the method (a) is preferable because a large amount of by-products such as low molecular weight compounds, higher-order condensates, and structural isomers are formed, and it is very difficult to isolate the target product. It's not a method. The methods (b) to (d) have been proposed as a method for producing a higher purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound in a high yield. In any of the methods, a highly pure 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound could not be produced with sufficiently satisfactory yield and production efficiency.

JP-A-5-4978 JP-A-8-53304 JP-A-8-208549 JP 63-2223020 A Japanese Patent Laid-Open No. 7-76538 Japanese Patent Laid-Open No. 7-173089 Japanese Patent Laid-Open No. 10-87537

  The present invention has been made in view of the above-described prior art, and produces a high-purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound with high yield and high efficiency. It is an object to provide a method.

  As a result of intensive studies to solve the above problems, the present inventors have made a reaction with a specific amount of acetonitrile in a method in which phenols and glyoxal or a glyoxal derivative are reacted in the presence of an acid catalyst, and the reaction temperature is reduced to 0. It has been found that a high-purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be obtained in a high yield by controlling in the range of ˜60 ° C. In purifying the obtained reaction mixture, a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be efficiently and simply used by using a mixed solvent of acetonitrile and water as a purification solvent. The inventors have found that they can be separated, and have completed the present invention.

  Thus, according to the present invention, there is a step of reacting a phenol with glyoxal or a glyoxal derivative in the temperature range of 0 to 60 ° C. in the presence of an acid catalyst and 5% by weight or more of acetonitrile with respect to the phenol. , Formula (1)

(In the formula, R represents a halogen atom or an organic group, and n represents an integer of 0 to 4. When n is 2 or more, R may be the same or different.) A process for producing a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound is provided.

In the manufacturing method of this invention, it is preferable that the usage-amount of acetonitrile is 10 to 30 weight% with respect to phenols.
In the production method of the present invention, it is preferable to react phenols with glyoxal or a glyoxal derivative at 0 to 40 ° C.
Moreover, it is preferable that the manufacturing method of this invention further has the process of refine | purifying the reaction mixture obtained by making phenols react with glyoxal or a glyoxal derivative using the mixed solvent of acetonitrile and water.

According to the present invention, a high-purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be produced with high yield and high production efficiency.
Therefore, the production method of the present invention is useful as a method for industrially mass-producing the 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound.

Hereinafter, the production method of the present invention will be described in detail.
In the method for producing a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound of the present invention, a phenol and glyoxal or a glyoxal derivative are mixed with 5% by weight or more of acetonitrile with respect to the acid catalyst and the phenol. It has the process made to react in the temperature range of 0-60 degreeC in presence.

The phenols used in the present invention are phenol and analogs thereof, and specifically, phenol compounds having 1 to 4 substituents at any position except the para position of the phenol or benzene ring.
Specifically, the phenols used in the present invention are compounds represented by the following.

(In the above formula, R represents a halogen atom or an organic group, and n represents an integer of 0 to 4, except that R is substituted at the para position of the hydroxyl group. R may be the same or different.

Examples of the halogen atom for R include fluorine, chlorine, bromine and the like.
Examples of the organic group include alkyl groups such as methyl group, ethyl group, propyl group, and isopropyl group; alkoxy groups such as methoxy group, ethoxy group, propoxy group, and isopropoxy group; phenyl group, 4-methylphenyl group, and the like. Examples thereof include a phenyl group which may have a substituent.

  Specific examples of phenol and its analogs include phenol; o-fluorophenol, m-fluorophenol, 2,6-difluorophenol, 3,5-difluorophenol, 2,3,5,6-tetrafluorophenol, o Halogen-substituted phenols such as chlorophenol, m-chlorophenol, 2,6-dichlorophenol, 3,5-dichlorophenol, o-bromophenol, m-bromophenol, 2,6-dibromophenol; o-cresol, Alkyl group-substituted phenols such as m-cresol, 2,3-xylenol, 2-ethylphenol and 3-ethylphenol; alkoxy such as 2-methoxyphenol, 3-methoxyphenol, 2,6-dimethoxyphenol and 2-ethoxyphenol Group-substituted phenol; 2 Phenyl-substituted phenols, such as phenylphenol; and the like.

  Of these, phenol is particularly preferred. When phenol is used, 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane useful as a host compound for an inclusion compound can be obtained.

  The usage-amount of phenols is 4-12 mol normally with respect to 1 mol of glyoxal or a glyoxal derivative, Preferably it is 4-6 mol. When the amount of phenol used is less than 4 mol, a large amount of higher-order condensate is formed, and the yield of 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound decreases, resulting in 12 mol. Exceeding this is not preferable because the residual amount of unreacted phenols increases, making it difficult to recover.

  Examples of the glyoxal or glyoxal derivative used in the present invention include glyoxal; 1,1,2,2-tetramethoxyethane, 1,1,2,2-tetraethoxyethane, 1,1,2,2-tetrapropoxyethane. Acetal derivatives of glyoxal such as 1,1,2,2-tetraallyloxyethane; and alkali metal sulfite adducts of glyoxal such as glyoxal sodium bissulfite. Among these, the use of glyoxal or 1,1,2,2-tetraallyloxyethane is preferable because the target product can be obtained with high yield and is easily available.

  The glioxal or glyoxal derivative can be used in any form of a solid or a solution. When using glioxal, it is usually used in the form of a commercially available 40% by weight aqueous solution.

  Examples of the acid catalyst used in the present invention include organic acids such as acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; solid acids such as acidic cation exchange resin Inorganic acids such as phosphoric acid, sulfuric acid, hydrochloric acid and perchloric acid; These acid catalysts can be used alone or in combination of two or more. Among these, the use of an inorganic acid is preferable and the use of sulfuric acid is more preferable because side reactions can be reduced.

The concentration of the acid catalyst to be used is not particularly limited, and various concentrations can be used, but a high concentration is preferable from the viewpoint of promptly performing the reaction. For example, when sulfuric acid is used as the acid catalyst, the use of 90% or more is preferable, and the use of 95% or more is particularly preferable.
The usage-amount of an acid catalyst is 2-6 gram equivalent normally with respect to 1 mol of glyoxal or a glyoxal derivative, Preferably it is 3-5 gram equivalent.

  In the present invention, acetonitrile is used as a reaction solvent. Acetonitrile having a purity of usually 90% by weight or more, preferably 95% by weight or more is used.

  The amount of acetonitrile used is usually 5% by weight or more, preferably 10 to 30% by weight, based on phenols. By using acetonitrile in such a use amount, side reactions can be suppressed and a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be obtained in a high yield.

  In the present invention, a mixture of acetonitrile and other solvent may be used as a reaction solvent. Other solvents to be used are not limited as long as they are inert to the reaction. For example, water; alcohols such as methanol, ethanol, propanol and isopropanol; ethers such as diethyl ether and tetrahydrofuran; Among these, use of a mixed solvent of water and acetonitrile is preferable.

  The reaction temperature between the phenol and glyoxal or glyoxal derivative is 0 to 60 ° C, preferably 0 to 40 ° C. In this temperature range, side reactions can be reduced and a high purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be produced in a high yield. If the reaction temperature is lower than 0 ° C., the amount of low-molecular compound produced is increased, and if it is higher than 60 ° C., the amount of higher-order condensate produced is increased, which is not preferable.

The method for reacting phenols with glyoxal or glyoxal derivatives is not particularly limited. For example,
(A) A method of dropping an acid catalyst while stirring a mixed solution of acetonitrile, phenols, glyoxal or glyoxal derivative,
(B) A method in which glyoxal or a glyoxal derivative (or a solvent solution thereof) is dropped while stirring a mixed solution of acetonitrile, phenols, and an acid catalyst.
(C) A method of dropping phenols (or a solvent solution of phenols) while stirring a mixed solution of acetonitrile, glyoxal or a glyoxal derivative and an acid catalyst, and the like.
Among these, the method (a) is preferable because the target product can be obtained with good yield.

In the method (b) or (c), the solvent used for the solvent solution of glyoxal or glyoxal derivative and the solvent solution of phenols is listed as water; acetonitrile and those that can be used as the reaction solvent. The thing similar to a thing is mentioned.

  When the method (a) is employed, the dropping rate of the acid catalyst is not particularly limited. For example, when concentrated sulfuric acid is used as the acid catalyst, the dropping rate of the acid catalyst is usually 0.01 to 3 gram equivalent / hr, preferably 0.1 to 0.3 gram equivalent / hr. When the dropping rate of the acid catalyst is too high, the production of by-products is promoted, and the purity and yield of the 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound tend to be lowered.

  The reaction time may be appropriately selected according to the reactivity of the raw materials and reaction conditions, but is usually from several minutes to several days, preferably from 1 to 100 hours. The completion of the reaction can be confirmed, for example, by sampling the reaction solution and using a known analysis means such as high performance liquid chromatography, gas chromatography, or thin layer chromatography.

  After completion of the reaction, the reaction is stopped by adding a base to the reaction solution and neutralizing it. The base used for the neutralization treatment is not particularly limited, and examples thereof include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; sodium carbonate, And carbonates such as potassium carbonate, magnesium carbonate, and calcium carbonate. Among these, sodium hydroxide is preferable from the viewpoint of production cost and the like. These can be used in the form of a solid or an aqueous solution, but are preferably used in an aqueous solution.

  After neutralization with a base, the target crude 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound is collected from the slurry-like reaction mixture by filtration. By refine | purifying the obtained crude crystal using a refinement | purification solvent, the crystal | crystallization of a highly purified 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be isolated.

  As a purification solvent to be used, a mixed solvent of acetonitrile and water is preferably used. By using a mixed solvent of acetonitrile and water as a purification solvent, the number of steps required for purification can be reduced, and a high purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound can be obtained from the reaction mixture. Can be isolated efficiently.

  The mixing ratio (volume ratio) of the mixed solvent of acetonitrile and water used as the purification solvent is usually 1:50 to 10: 1, preferably 1:10 to 1: 1, more preferably 1: 5 to 1: 1. is there.

When a mixed solvent of acetonitrile and water is used as a purification solvent, purification can be performed by repeating washing of crude crystals and filtration.
The method for washing the crude crystals is not particularly limited, but is preferably heated and stirred. In this case, the heating temperature is usually 40 to 80 ° C, preferably 50 to 70 ° C. Moreover, stirring time is 0.1 to 5 hours normally, Preferably it is 0.1 to 1 hour.

  After heating and stirring, the stirring solution is returned to room temperature, and the crystals are collected by filtration. This operation is usually repeated 1 to 5 times, preferably 1 to 2 times. After purification, the obtained crystals are dried to obtain a high purity 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound.

  The 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound obtained as described above is a compound represented by the formula (1). In formula (1), R and n represent the same meaning as described above. In the present invention, among the compounds represented by the formula (1), 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane is particularly preferable.

  The 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound obtained by the production method of the present invention includes an inclusion compound host compound, a heat-resistant epoxy resin production raw material, an epoxy resin curing agent, and a photoresist. It is useful as a raw material for related photosensitive ballast agents, cresol novolak resin modifiers, antioxidants and the like.

  EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to this.

Example 1 Production of 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane (1)
A four-necked flask equipped with a stirrer, a cooling tank and a thermometer was prepared, and 15 g (150 g / mol) of acetonitrile was added to the flask and cooled to 3 ° C. 56.47 g (0.6 mol) of phenol was added, and 14.51 g (0.1 mol) of 40% aqueous glyoxal solution was further added. The temperature in the flask was raised to 15 ° C., and 20.43 g (0.2 mol) of 96% sulfuric acid was added dropwise over 2 hours, followed by stirring at 15 ° C. for 25 hours.

30 ml of acetonitrile and 30 ml of water were added to the reaction solution, and 58.0 g (0.41 mol) of a 28% aqueous sodium hydroxide solution was added dropwise at 35 ° C. or lower to the resulting mixture to make the pH neutral. The precipitated crystals were collected by filtration, washed with 100 ml of water, and then washed with 150 ml of acetonitrile: water = 1: 2 (volume ratio). Thereafter, the washed crystal was transferred to another container, 80 ml of acetonitrile and 80 ml of water were added, and the mixture was heated and stirred at 60 ° C. for 30 minutes. The stirred product was cooled to 15 ° C., and the crystals were collected by filtration. The crystals collected by filtration were washed with 30 ml of a mixed solution of acetonitrile: water = 1: 2 (volume ratio) and filtered again.
The obtained crystals were dried under reduced pressure conditions of 130 ° C. and 0.7 kPa for 4 hours to obtain 16.80 g of 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane (yield 42.16%, (99% by weight purity) was obtained as white crystals.

Example 2 Production of 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane (2)
9 g (150 g / mol) of acetonitrile was placed in a flask, cooled to 3 ° C., added with 33.31 g (0.33 mol) of phenol, and then maintained at 3 ° C. to 7 ° C. while maintaining 1,3,2,2-tetraallyl. 14.1 g (0.055 mol) of oxyethane was added. Thereafter, the temperature was raised to 15 ° C., and 11.33 g (0.11 mol) of 96% sulfuric acid was added dropwise over 2 hours, followed by stirring at 15 ° C. for 25 hours.

15 ml of acetonitrile and 15 ml of water were added to the reaction solution, and 29.0 g (0.203 mol) of 28% aqueous sodium hydroxide solution was added dropwise to the resulting mixture at 35 ° C. or lower to make the pH neutral. The precipitated crystals were collected by filtration, washed with 50 ml of water, and then washed with 75 ml of acetonitrile: water = 1: 2 (volume ratio). Thereafter, the obtained crystal was transferred to another container, 40 ml of acetonitrile and 40 ml of water were added, and the mixture was heated and stirred at 60 ° C. for 30 minutes. The stirred product was cooled to 15 ° C., and the crystals were collected by filtration. The collected crystals were washed with 15 ml of a composition of acetonitrile: water = 1: 2, and filtered again.
The obtained crystals were dried under reduced pressure conditions of 130 ° C. and 0.7 kPa for 4 hours to obtain 8.1 g of 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane (yield 36.6%, (99% by weight purity) was obtained as white crystals.

Comparative Example 1
A reaction was carried out in the same manner as in Example 1 except that acetone was used instead of acetonitrile. As a result, 8.77 g of 1,1,2,2- (4-hydroxyphenyl) ethane (yield: 21.3%, A purity of 97% by weight) was obtained.
Further, in this case, filtration operation was required three times in order to use methanol for purification and achieve a purity of 97%.

Comparative Example 2
A reaction was carried out in the same manner as in Example 1 except that toluene was used instead of acetonitrile. As a result, 12.05 g of 1,1,2,2- (4-hydroxyphenyl) ethane (yield 26.2%, A purity of 86.6% by weight) was obtained.
In this case, acetone was used for purification, but the filtration operation was difficult.

Claims (4)

Formula (1) having a step of reacting phenols with glyoxal or a glyoxal derivative in the temperature range of 0 to 60 ° C. in the presence of an acid catalyst and 5% by weight or more of acetonitrile with respect to the phenols.

(In the formula, R represents a halogen atom or an organic group, and n represents an integer of 0 to 4. When n is 2 or more, R may be the same or different.)
The manufacturing method of the 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound shown by these.   The method for producing a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound according to claim 1, wherein the amount of acetonitrile used is 10 to 30% by weight based on phenols.   The method for producing a 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound according to claim 1 or 2, wherein a phenol and glyoxal or a glyoxal derivative are reacted at 0 to 40 ° C. . The neutralizing reaction mixture obtained by reacting phenols with glyoxal or a glyoxal derivative and further washing the precipitated crude crystals with a mixed solvent of acetonitrile and water . The manufacturing method of the 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane compound as described in 1 above.