JPH10158235A - Purification of 4,4'-dihydroxydiphenyl sulfone monoether derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily and efficiently purity a 4,4'-dihydroxydiphenyl sulfone monoether derivative in high purity and high yield by depositing an alkaline metal salt of the derivative from a mixture containing 4,4'-dihydroxydiphenyl sulfone and the monoether derivative therefrom. SOLUTION: This method for purification comprises adding an alkaline metal ion source (particularly preferably, potassium ion source) to an aqueous solution of a mixture containing an alkaline metal salt of 4,4'-dihydroxydiphenyl sulfone and 4,4'-dihydroxydiphenyl sulfone monoether derivative shown by the formula (R is an alkyl, alkenyl, aralkyl or cycloaralkyl, preferably, aralkyl), to deposit the alkaline metal salt of the monoether derivative of the formula for separation, and subsequently subjecting the separated compound to acid treatment.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] The present invention provides a novel purification method capable of purifying a derivative containing 4,4'-dihydroxydiphenylsulfone and a monoether derivative thereof in high purity and high yield, and a purification intermediate of the purification method. The present invention relates to a novel production method capable of obtaining a body with high purity and high yield.

[0002]

[Prior art]

 General formula

[0003]

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Wherein R is an alkyl group, an alkenyl group,
It represents an aralkyl group or a cycloalkyl group. The 4,4'-dihydroxydiphenylsulfone monoether derivative represented by the formula (1) is useful as a developer for a thermosensitive recording material.

[0005] The above monoether derivative is generally prepared by a reaction formula

[0006]

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(Wherein, R is the same as above, and X represents a halogen atom.) As shown in an aqueous solvent in the presence of an alkali such as an alkali metal hydroxide or an alkali metal carbonate, It is synthesized by reacting 4'-dihydroxydiphenyl sulfone with an alkylating agent such as an alkyl halide or benzyl halide. Here, a chlorine atom, a bromine atom, an iodine atom and the like are used as the halogen atom.

However, since 4,4'-dihydroxydiphenyl sulfone has two hydroxyl groups, the composition of the product can be changed by variously changing the reaction conditions, but the monoether derivative is selectively formed by the above reaction. It is extremely difficult, and usually, it is obtained as a reaction mixture containing, in addition to the monoether derivative (I), the diether derivative (II), unreacted 4,4'-dihydroxydiphenylsulfone, a small amount of a nuclear substituent, and the like.

Therefore, the desired monoether derivative (I)
In order to obtain high purity, some separation / purification operation is required.

In this case, the diether derivative (II) has a low solubility in a polar solvent such as water due to its nature, but has a high solubility in a non-polar solvent. Easily soluble in organic solvents. Therefore, by performing solvent extraction, filtration, adsorbent treatment, etc., with an aqueous alkali solution having a concentration sufficient to dissolve the monoether derivative (I) and unreacted 4,4′-dihydroxydiphenyl sulfone,
The diether derivative (II) can be easily removed. However, the monoether derivative (I) and unreacted 4,
Since 4'-dihydroxydiphenyl sulfone has a phenolic hydroxyl group, it remains dissolved in an aqueous alkaline solution, and it is not easy to efficiently separate only the monoether derivative (I) from it with high yield. .

Conventionally, as a method for separating the desired monoether derivative (I) from a mixture containing the monoether derivative (I) and unreacted 4,4'-dihydroxydiphenylsulfone, a method by column chromatography ( JP-A-58-20493, JP-A-58-82788), a method of removing only unreacted substances from an organic solvent solution of the mixture by transferring the mixture to an aqueous hydrogen carbonate solution (JP-A-60-56949), A method by selective extraction using an organic solvent such as alcohol and ketone (Japanese Patent Application Laid-Open No. 3-258760) is known.

However, these methods have low separation / purification efficiency, are complicated in steps, have problems in terms of work and environment due to the use of an organic solvent, and have insufficient purity of the target compound obtained. There are various disadvantages.

[0013]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned drawbacks of the prior art and to provide a simpler operation for 4,4 '.
An object of the present invention is to provide a purification method capable of efficiently purifying a derivative containing dihydroxydiphenylsulfone and a monoether derivative thereof with high purity and high yield.

[0014]

Means for Solving the Problems The present inventor has made intensive studies to achieve the above object. In particular, the solubility and salting-out effect of 4,4'-dihydroxydiphenyl sulfone and its monoether derivative in an aqueous solution of each alkali metal ion were studied.

As a result, the solubility of 4,4'-dihydroxydiphenylsulfone and its monoether derivative in an aqueous alkali metal ion solution is greatly different. Particularly, as the concentration of the alkali metal ion increases, the solubility of the monoether derivative greatly decreases. A phenomenon that has never been known before. The present inventor has further continued his research based on the above phenomenon. As a salting-out agent, an alkali metal ion donor was added to an aqueous solution of an alkali metal salt of 4,4′-dihydroxydiphenyl sulfone and an alkali metal salt of a monoether derivative thereof. It has been found that the salting out by adding the compound efficiently precipitates the alkali metal salt of the monoether derivative, and that the above object can be achieved by separating and subjecting to an acid treatment. The present invention has been completed based on these new findings.

That is, the present invention relates to an alkali metal salt of 4,4'-dihydroxydiphenyl sulfone and a compound of the formula (I)
An alkali metal ion donor is added to an aqueous solution of a mixture containing an alkali metal salt of a 4,4'-dihydroxydiphenylsulfone monoether derivative represented by the formula to precipitate an alkali metal salt of a monoether derivative of the general formula (I). ,
Separating, followed by acid treatment, 4,
Purification method of 4'-dihydroxydiphenylsulfone monoether derivative, alkali metal salt of 4,4'-dihydroxydiphenylsulfone and alkali metal of 4,4'-dihydroxydiphenylsulfone monoether derivative represented by general formula (I) 4,4'-dihydroxydiphenyl sulfone monoether, wherein an alkali metal ion donor is added to an aqueous solution of a mixture containing a salt to precipitate and separate an alkali metal salt of a monoether derivative of the general formula (I). The present invention relates to a method for producing an alkali metal salt of a derivative.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, preferred alkali metals include potassium and sodium.

The alkyl group represented by R in the general formula (I) includes, for example, methyl, ethyl, n-propyl, isopropyl, butyl, hexyl and the like. Examples of the alkenyl group include propenyl and vinyl. Examples of the aralkyl group include a benzyl group and a phenethyl group. Examples of the cycloalkyl group include cyclohexyl and cyclopentyl. Of these, R is preferably an alkyl group.

One example of the relationship between the solubility of 4,4'-dihydroxydiphenyl sulfone and its monoether derivative in an aqueous alkali metal ion solution and the concentration of the alkali metal ion is shown in FIGS.

FIG. 1 shows the solubility of 4,4'-dihydroxydiphenylsulfone or 4-isopropyloxy-4'-hydroxydiphenylsulfone in an aqueous potassium ion solution at room temperature, using potassium hydroxide (KOH),
Potassium bromide (KBr) or potassium acetate (KOAc)
Is shown as a solubility curve when using as a potassium ion supplier. Here, 4,4'-dihydroxydiphenylsulfone dissolves as a monopotassium salt or dipotassium salt, and 4-isopropyloxy-4'-hydroxydiphenylsulfone dissolves as a monopotassium salt.

FIG. 1 shows that 4,4′-dihydroxydiphenylsulfone is very well soluble in an aqueous solution of potassium ion, whereas 4-isopropyloxy-4′-hydroxydiphenylsulfone is a type of potassium ion donor. Regardless, the solubility is very low, and it is clear that it hardly dissolves particularly at a potassium ion concentration of about 7% by weight or more.

Similarly, FIG. 2 shows the solubility of 4,4'-dihydroxydiphenylsulfone or 4-isopropyloxy-4'-hydroxydiphenylsulfone in an aqueous sodium ion solution at room temperature. It is shown as a solubility curve when used as an ion supplier. Here, 4,4'-dihydroxydiphenylsulfone dissolves as a monosodium salt or disodium salt, and 4-isopropyloxy-4'-hydroxydiphenylsulfone dissolves as a monosodium salt.

From FIG. 2, it can be seen that 4,4'-dihydroxydiphenylsulfone dissolves quite well in aqueous sodium ion solution, whereas 4-isopropyloxy-4'-hydroxydiphenylsulfone has much lower solubility.
In particular, it is apparent that almost no dissolution occurs at a sodium ion concentration of about 10% by weight or more.

The present invention utilizes the difference in solubility as shown in FIG. 1 and FIG. 2 to make use of the alkali metal salt of 4,4′-dihydroxydiphenyl sulfone and the 4,4′-formula represented by the general formula (I). An alkali metal ion donor acting as a salting-out agent is added to an aqueous solution of a mixture containing an alkali metal salt of a dihydroxydiphenylsulfone monoether derivative to precipitate and separate an alkali metal salt of a monoether derivative of the general formula (I). In particular, it has the greatest features.

The aqueous solution of the above mixture to which the purification method of the present invention is applied includes an alkali metal salt of 4,4′-dihydroxydiphenyl sulfone and 4,4′-dihydroxydiphenylsulfone represented by the general formula (I):
There is no particular limitation as long as it is a mixed aqueous solution of an alkali metal salt of a 4′-dihydroxydiphenylsulfone monoether derivative. As a specific example, usually, the diether derivative (II) is removed from the reaction mixture shown in the above reaction formula,
Alkali which is a mixture mainly composed of an alkali metal salt of 4,4'-dihydroxydiphenylsulfone and an alkali metal salt of a 4,4'-dihydroxydiphenylsulfone monoether derivative of the general formula (I) and containing a small amount of a nuclear substituent An aqueous solution of a metal ion can be mentioned as a preferable one, but is not limited thereto, and it is a matter of course that the method of the present invention can be applied to a similar mixture obtained by other methods.

The alkali metal ion donor to be added to the aqueous solution of the above mixture is not particularly limited as long as it is a compound which dissolves in water to generate an alkali metal ion. Specifically, for example, potassium hydroxide, potassium carbonate, potassium chloride, potassium bromide, potassium sulfate, potassium nitrate, water-soluble inorganic potassium compounds such as potassium phosphate, potassium acetate, water-soluble organic potassium compounds such as potassium formate, Examples thereof include water-soluble inorganic sodium compounds such as sodium hydroxide, sodium carbonate, sodium chloride, sodium bromide, sodium sulfate, sodium nitrate, and sodium phosphate, and water-soluble organic sodium compounds such as sodium acetate and sodium formate.

When an alkali metal ion donor is added to the aqueous solution of the above mixture, the donor may be added in a solid state or as a concentrated aqueous solution. The amount used is a sufficient difference between the solubility of the alkali metal salt of 4,4'-dihydroxydiphenylsulfone and the solubility of the alkali metal salt of the 4,4'-dihydroxydiphenylsulfone monoether derivative of the general formula (I). Is the final concentration of the alkali metal ion such that For example, in the case of a mixture of potassium 4,4'-dihydroxydiphenylsulfone and a potassium salt of its monoether derivative, the final concentration of potassium ion is about 7% by weight or more, as apparent from the description of FIG. Preferably 8
It is desirable to add a potassium ion donor so as to have a concentration of about 20% by weight. Also, for example, 4, 4 '
-In the case of a mixture of sodium salt of dihydroxydiphenylsulfone and a sodium salt of its monoether derivative, the final concentration of sodium ion is about 10% by weight or more, preferably 11 to
It is desirable to add a sodium ion donor so as to have a concentration of about 15% by weight.

As the alkali metal ion donor, those corresponding to the alkali metal species of the above alkali metal salts, for example, potassium ion donor if the alkali metal salt is potassium salt, and sodium ion donor if the alkali metal salt is sodium salt It is preferable to use a body from the viewpoint of separation efficiency.

Further, the difference between the solubility of the alkali metal salt of 4,4′-dihydroxydiphenylsulfone and the solubility of the alkali metal salt of the 4,4′-dihydroxydiphenylsulfone monoether derivative of the general formula (I) is larger, In addition, it is particularly preferable to use a potassium ion donor as the alkali metal ion donor from the viewpoint that the crystal form of the monoether derivative alkali metal salt to be precipitated is excellent.

By adding an alkali metal ion donor to an aqueous solution of the above mixture, the compound of the general formula (I) having low solubility is obtained.
The alkali metal salt of the 4,4'-dihydroxydiphenylsulfone monoether derivative is precipitated by salting out, and is separated and collected by a conventional method such as filtration, centrifugation, decantation and the like.

Here, the alkali metal salt is usually 90
% And a high purity of 90% or more. Therefore, a suitable purified intermediate for the purification of the monoether derivative can be produced with high purity and high yield.

When it is desired to further increase the purity of the obtained alkali metal salt of the 4,4'-dihydroxydiphenylsulfone monoether derivative, this is dissolved in water, and an alkali metal ion donor is added again to carry out salting out. Just do
Thereby, an extremely high purity product can be obtained.

Next, the desired 4,4'-dihydroxydiphenylsulfone monoether derivative is treated with an acid to treat the alkali metal salt of the 4,4'-dihydroxydiphenylsulfone monoether derivative obtained above with high purity. Can be obtained in high yield.

The acid treatment may be carried out according to a conventional method. The alkali metal salt of the monoether derivative is dissolved in about 2 to 10 times, preferably about 3 to 5 times the amount of water, and if necessary, activated carbon treatment is carried out. After that, an inorganic acid such as sulfuric acid or hydrochloric acid or an organic acid such as acetic acid is added to adjust the pH to about 1 to 9, preferably 3 to 10.
It is performed almost quantitatively by separating the free monoether derivative to be precipitated by filtration or the like.

Thus, the desired 4,4'-dihydroxydiphenylsulfone monoether derivative can be purified with high purification yield and high purity.

[0036]

The present invention will be further clarified with reference to the following examples.

Example 1 60.0 g of 4,4'-dihydroxydiphenyl sulfone
(0.24 mol), 26.9 g of potassium hydroxide (0.
48 mol) was added to 60 g of water, and while keeping the temperature at 70 ° C., 29.5 g (0.24 mol of isopropyl bromide) was added.
l) was added dropwise over 1 hour. At the end of the dropwise addition, the mixture was refluxed at an internal temperature of 55 ° C. The reaction is allowed to stand for a further 15 hours
Reflux at 72 ° C. Thus, 4-isopropyloxy-4′-hydroxydiphenyl sulfone was synthesized. When the composition of the product at this stage was analyzed by HPLC, 4-isopropyloxy-4′-hydroxydiphenylsulfone: 4,4′-diisopropyloxydiphenylsulfone: 4,4′-dihydroxydiphenylsulfone = 74.9: 3.1: 22.0 (% by weight).

The reaction mixture was charged with potassium hydroxide 5.0.
g (0.09 mol), water 150 g, toluene 120 m
and 4-isopropyloxy-4'-hydroxydiphenylsulfone and unreacted 4,4'-dihydroxydiphenylsulfone are dissolved in an aqueous phase, and a toluene phase in which 4,4'-diisopropyloxydiphenylsulfone is dissolved. Was removed by liquid separation. At this time, the potassium ion concentration in the aqueous phase was 5% by weight.

Further, 12.6 potassium hydroxide was added to the aqueous phase.
g (0.22 mol), stirred overnight, cooled to room temperature, and precipitated the potassium salt of 4-isopropyloxy-4′-hydroxydiphenylsulfone. At this time, the potassium ion concentration in the aqueous phase was 8% by weight. This was filtered to obtain 80.7 g of the potassium salt white crystals (wet cake state). The composition of the obtained crystal was
When analyzed by PLC, 4-isopropyloxy-4′-
Hydroxydiphenylsulfone: 4,4'-diisopropyloxydiphenylsulfone: 4,4'-dihydroxydiphenylsulfone = 95.2: 0.1: 4.7 (% by weight).

The crystals were dissolved in 400 ml of water and treated with activated carbon, and the pH was adjusted to 7 with sulfuric acid. The precipitated crystals were filtered and dried to give 4-isopropyloxy-4'-hydroxydiphenylsulfone. 0.5 g was obtained. When the composition of the obtained crystal was analyzed by HPLC,
-Isopropyloxy-4'-hydroxydiphenylsulfone: 4,4'-diisopropyloxydiphenylsulfone: 4,4'-dihydroxydiphenylsulfone =
96.0: 0.1: 3.9 (% by weight). The yield from the starting materials in the synthesis was 72.0%, and the purification yield in the purification step was 96%.

Example 2 Using the wet cake of potassium salt of 4-isopropyloxy-4'-hydroxydiphenylsulfone having a purity of 95.2% obtained in Example 1, a second purification by salting out was carried out.

That is, 80.7 g of the above wet cake was dissolved in 150 g of water, and 27.0 g (0.4 wt.
8 mol), and a potassium salt of 4-isopropyloxy-4′-hydroxydiphenylsulfone was similarly precipitated. At this time, the potassium ion concentration was 10% by weight. This was filtered to obtain 74.7 g of the potassium salt as white crystals (wet cake state). The composition of the obtained crystals was analyzed by HPLC to find that 4-isopropyloxy-4′-hydroxydiphenylsulfone:
4,4'-diisopropyloxydiphenyl sulfone:
4,4'-dihydroxydiphenyl sulfone = 99.
8: 0.0: 0.2 (% by weight).

The crystals were dissolved in 400 ml of water and treated with activated carbon, and the pH was adjusted to 7 with sulfuric acid.
49.0 g of 4'-hydroxydiphenyl sulfone was obtained. When the composition of the obtained crystal was analyzed by HPLC,
-Isopropyloxy-4'-hydroxydiphenylsulfone: 4,4'-diisopropyloxydiphenylsulfone: 4,4'-dihydroxydiphenylsulfone =
99.9: 0.0: 0.1 (% by weight). This 2
The purification yield in the purification step by the second salting out was 97%.

Example 3 8.5 g (0.029 mol) of 4-isopropyloxy-4'-hydroxydiphenylsulfone and 4,4'-
1.5 g of dihydroxydiphenyl sulfone (0.006
50.0 g of water and 2.4 g (0.043 mol) of potassium hydroxide were added to the mixture, and the mixture was heated to 70 ° C. and dissolved.

To this solution was added 7.0 g of potassium hydroxide.
(0.12 mol), the mixture was stirred overnight, cooled to room temperature, and the potassium salt of 4-isopropyloxy-4′-hydroxydiphenylsulfone was precipitated. At this time, the potassium ion concentration was 9% by weight. This is filtered,
After drying, 10.5 g of white crystals of the potassium salt were obtained.
When the composition of the obtained crystal was analyzed by HPLC, 4-isopropyloxy-4′-hydroxydiphenylsulfone: 4,4′-dihydroxydiphenylsulfone = 9
9.0: 1.0 (% by weight).

The crystals were dissolved in 50 ml of water, treated with activated carbon, and the pH was adjusted to 7 with sulfuric acid. The precipitated crystals were filtered and dried to give 4-isopropyloxy.
8.2 g of 4'-hydroxydiphenyl sulfone was obtained.
When the composition of the obtained crystal was analyzed by HPLC, 4-isopropyloxy-4′-hydroxydiphenylsulfone: 4,4′-dihydroxydiphenylsulfone = 9
9.2: 0.8 (% by weight). 96% purification yield
Met.

Example 4 8.0 g (0.027 mol) of 4-isopropyloxy-4'-hydroxydiphenylsulfone and 4,4'-
2.0 g of dihydroxydiphenyl sulfone (0.008
47.1 g of water and 5.6 g (0.049 mol) of a 48.6% by weight aqueous potassium hydroxide solution were added to the mixture, and the mixture was heated to 70 ° C. and dissolved.

To this solution was added 20.0 g of potassium bromide.
(0.168 mol), the mixture was stirred overnight, cooled to room temperature, and the potassium salt of 4-isopropyloxy-4′-hydroxydiphenylsulfone was precipitated. At this time, the potassium ion concentration was 10% by weight. This was filtered and dried to obtain 9.3 g of white crystals of the potassium salt. When the composition of the obtained crystal was analyzed by HPLC,
-Isopropyloxy-4'-hydroxydiphenylsulfone: 4,4'-dihydroxydiphenylsulfone =
98.8: 1.2 (% by weight).

The crystals were dissolved in 50 ml of water, treated with activated carbon, and the pH was adjusted to 7 with sulfuric acid. The precipitated crystals were filtered and dried to give 4-isopropyloxy.
7.7 g of 4'-hydroxydiphenyl sulfone was obtained.
When the composition of the obtained crystal was analyzed by HPLC, 4-isopropyloxy-4′-hydroxydiphenylsulfone: 4,4′-dihydroxydiphenylsulfone = 9
9.2: 0.8 (% by weight). 96% purification yield
Met.

Example 5 8.0 g (0.027 mol) of 4-isopropyloxy-4'-hydroxydiphenylsulfone and 4,4'-
2.0 g of dihydroxydiphenyl sulfone (0.008
mol), 47.3 g of water and 5.6 g (0.049 mol) of a 48.6% by weight aqueous potassium hydroxide solution were added, and the mixture was heated to 70 ° C. and dissolved.

To this solution was added 16.8 g of potassium acetate.
(0.171 mol), the mixture was stirred overnight, cooled to room temperature, and the potassium salt of 4-isopropyloxy-4′-hydroxydiphenylsulfone was precipitated. At this time, the potassium ion concentration was 10% by weight. This was filtered and dried to obtain 9.4 g of white crystals of the potassium salt. When the composition of the obtained crystal was analyzed by HPLC,
-Isopropyloxy-4'-hydroxydiphenylsulfone: 4,4'-dihydroxydiphenylsulfone =
99.4: 0.6 (% by weight).

The crystals were dissolved in 50 ml of water, treated with activated carbon, and the pH was adjusted to 7 with sulfuric acid.
7.8 g of 4'-hydroxydiphenyl sulfone was obtained.
When the composition of the obtained crystal was analyzed by HPLC, 4-isopropyloxy-4′-hydroxydiphenylsulfone: 4,4′-dihydroxydiphenylsulfone = 9
9.6: 0.4 (% by weight). Purification yield 98%
Met.

[0053]

According to the method of the present invention, a derivative containing 4,4'-dihydroxydiphenylsulfone and a monoether derivative thereof can be purified with high purity by a simple operation without using an organic solvent. An extraordinary effect is obtained in that purification can be performed very efficiently with high yield.

[Brief description of the drawings]

BRIEF DESCRIPTION OF DRAWINGS FIG. 1 shows the solubility of 4,4′-dihydroxydiphenylsulfone or 4-isopropyloxy-4′-hydroxydiphenylsulfone in an aqueous potassium ion solution at room temperature using potassium hydroxide, potassium bromide or potassium acetate. It is shown as a solubility curve when used as an ion supplier.

FIG. 2 shows the solubility of 4,4′-dihydroxydiphenylsulfone or 4-isopropyloxy-4′-hydroxydiphenylsulfone in an aqueous sodium ion solution at room temperature when sodium hydroxide was used as a sodium ion donor. Is shown as a solubility curve.

Claims (4)

[Claims] An alkali metal salt of 4,4'-dihydroxydiphenylsulfone and a compound of the general formula (In the formula, R represents an alkyl group, an alkenyl group, an aralkyl group or a cycloalkyl group.)
An alkali metal ion donor is added to an aqueous solution of a mixture containing an alkali metal salt of a dihydroxydiphenylsulfone monoether derivative to precipitate and separate an alkali metal salt of a monoether derivative of the general formula (I), which is then treated with an acid. A method for purifying a 4,4′-dihydroxydiphenylsulfone monoether derivative. 2. The method according to claim 1, wherein R is an alkyl group. 3. The alkali metal ion supplier is a potassium ion supplier, and the final concentration of potassium ion is 7% by weight.
The purification method according to claim 1, which is the above. 4. An alkali metal salt of 4,4'-dihydroxydiphenylsulfone and a compound represented by the general formula: (In the formula, R represents an alkyl group, an alkenyl group, an aralkyl group or a cycloalkyl group.)
An alkali metal ion donor is added to an aqueous solution of a mixture containing an alkali metal salt of a dihydroxydiphenylsulfone monoether derivative to precipitate and separate an alkali metal salt of a monoether derivative of the general formula (I). For producing alkali metal salts of 4,4'-dihydroxydiphenylsulfone monoether derivatives.