CN1318399C - Processes for the preparation of diphenylsulfone compounds - Google Patents

Abstract

A process by which a high-purity 4,4'-dihydroxydiphenyl sulfone monoether can be industrially advantageously obtained. The process, which is for producing a compound represented by the formula (I) (I) (wherein R<1> and R<2> each independently represents halogeno, C1-8 alkyl, or C2-8 alkenyl; m and n each independently is an integer of 0 to 4; and R<3> represents C1-8 alkyl, C2-8 alkenyl, C3-8 cycloalkyl, or optionally substituted aralkyl), comprises (1) conducting pH adjustment two or more times in a purification step, (2) removing the alkyl halide used in excess, (3) using a solvent, e.g., water, having an iron content of 0.05 ppm or lower, (4) using a vessel coated inside with a corrosion-resistant layer, (6) adding a chelating agent, and (7) using a means for drying with mechanical stirring.

Description

Process for preparing diphenylsulfone compounds

Technical field:

The present invention relates to a process for the preparation of 4,4'-dihydroxydiphenylsulfone monoethers useful as developers for thermal recording agents.

Background technique:

Dihydroxydiphenylsulfone monoether is a developer excellent in coloring sensitivity, preservability, heat resistance and other properties, and is often used for thermal recording paper for faxes, bar codes, receipts and the like.

Among dihydroxydiphenylsulfone monoethers, such as 4-alkoxy-4'-hydroxydiphenylsulfone (hereinafter referred to as target compound), through 4,4'-dihydroxydiphenylsulfone (hereinafter referred to as As BPS) and halogen compounds such as alkyl halides in polar solvents such as dimethylformamide, dimethyl sulfoxide and alcohol in the presence of a base to prepare the method has been disclosed in Japanese Patent Application Publication No. - Zhao 58- 20493, Zhao 58-82788, Zhao 60-13852, Zhao 60-56949 and Heping 6-25148. A disadvantage of these methods is that they are difficult to improve reaction selectivity because solvents which dissolve the reaction reagents and reaction products very well are used. One problem is the production of significant amounts of the diether derivative by-product, 4,4'-dihydroxydiphenylsulfone diether.

WO 91/11433 discloses BPS and alkyl halide in 0.3-1.5 parts by weight (relative to 1 part by weight 4,4'-dihydroxydiphenyl sulfone) in an aqueous solvent of 1.5-3mol (relative to 1mol BPS) The reaction in the presence of base can obtain satisfactory results in both selectivity and yield.

Japanese Patent Application Laid-Open No. Hei 3-258760 describes a method for separating BPS from 4-alkoxy-4'-hydroxydiphenyl sulfone, wherein an immiscible aqueous alkali solution and alcohol or ketone are added with A mixture containing BPS and 4-alkoxy-4'-hydroxydiphenylsulfone is mixed, 4-alkoxy-4'-hydroxydiphenylsulfone goes into the organic layer, and the alkali metal salt of BPS goes into the aqueous layer to achieve separation.

In Japanese Patent Application Laid-Open No. Hei 60-56949, a method for the purification of 4-alkoxy-4'-hydroxydiphenyl sulfone is described, wherein BPS is alkylated or produced by other methods containing 4-alkane A solution of oxy-4'-hydroxydiphenylsulfone and unreacted BPS in a water-immiscible organic solvent is shaken with an aqueous bicarbonate solution to move the BPS into the water for separation.

Japanese Patent Application Laid-Open No. Hei 5-255234 describes a process for the production of 4-alkoxy-4'-hydroxydiphenyl sulfone, in which 4-alkoxy-4'-hydroxyl is produced by reacting BPS with an alkyl halide In the diphenyl sulfone method, an alkyl halide is added to a biphasic solvent system consisting of an aqueous solution of a basic compound (in which BPS is dissolved) and a water-immiscible organic solvent, and the basic compound is added to maintain the pH 7.5-9.5.

Japanese Patent Application Publication No. Hei 10-158235 has disclosed a method for purifying 4-alkoxy-4'-hydroxydiphenyl sulfone, wherein an alkali metal ion donor is added to a compound containing BPS alkali metal salt and 4-alkoxy in an aqueous solution of a mixture of alkali metal salts of 4-alkoxy-4'-hydroxydiphenylsulfones in order to deposit and isolate the alkali metal salts of 4-alkoxy-4'-hydroxydiphenylsulfones, followed by treatment of the salts with an acid.

In the above production method, as side reactions proceed simultaneously, the reaction solution contains the target compound and unreacted BPS, by-product 4,4'-dialkoxydiphenyl sulfone and other impurities. These impurities impair the performance of the product when used as a developer. Therefore, a purification method for removing impurities from the reaction solution is required.

Among these impurities, 4,4'-dialkoxydiphenyl sulfone (insoluble in water) can be removed by turning the reaction solution into an alkaline aqueous solution, adding a water-immiscible organic solvent, and extracting the sulfone to the organic layer for separation.

In order to remove unreacted BPS, a water-immiscible organic solvent was added to the reaction solution to form a two-phase system consisting of an organic layer and an aqueous layer, and the pH of the aqueous layer was adjusted to a predetermined value to allow the target compound to enter the organic layer. layer, while BPS went into the aqueous layer, and the organic layer was separated, washed with water if necessary and then cooled, and the deposited crystals were separated by filtration, thereby obtaining the target compound. This separation/purification method takes advantage of the difference in acidity between the BPS and the phenolic hydroxyl groups of the target compound.

Invention disclosure:

However, the difference in acidity between BPS and the phenolic hydroxyl groups of the target compound is subtle. If the pH of the aqueous layer is higher than a predetermined value, BPS is completely removed. Then, it is difficult to completely separate the target compound into the organic layer, resulting in a large loss of the target compound. Conversely, if the pH of the aqueous layer is lower than a predetermined value, the loss of the target compound is small. However, there is a problem that the BPS enters into the organic layer to be mixed into the target compound as an impurity.

As mentioned above, the 4,4'-dihydroxydiphenylsulfone monoethers produced by the prior art methods are not satisfactory in terms of purity. Especially when the reaction solution obtained from the reaction of a high-concentration raw material is purified according to the above method, BPS often tends to be mixed into the target compound as an impurity because the purification is insufficient.

4,4'-Dihydroxydiphenylsulfone monoether is mainly used as a developer. However, the problem is that if 0.4% or more of BPS is contained in 4,4'-dihydroxydiphenyl sulfone monoether, the so-called background fogging phenomenon, that is, the surrounding area of the heated part on the thermal recording paper, will occur. coloring. Therefore, it has been sought to develop some production methods for separating high-purity 4,4'-dihydroxydiphenylsulfone monoether.

When producing 4,4'-dihydroxydiphenylsulfone monoether on an industrial scale, the reaction solution sometimes becomes colored. In this case, the product 4,4'-dihydroxydiphenylsulfone monoether is also colored. It is sometimes difficult to completely decolorize (remove coloring substances) the product even if a decolorization and purification method using activated carbon or the like is performed thereafter. Another problem is the need for new methods of removing added decolorizing agents.

As described above, 4,4'-dihydroxydiphenylsulfone monoether is mainly used as a developer. Because of the purpose for which they are used, developers are not satisfactory even if they are slightly colored.

It is therefore necessary to establish an industrial process for producing uncolored, high-purity 4,4'-dihydroxydiphenylsulfone monoethers in high yields.

In addition, when 4,4'-dihydroxydiphenylsulfone monoether is taken out as crystals at the final stage and the crystals are dried by a heat drier, the crystals become lumps, so that the solvent cannot be completely removed. Monoethers containing solvents have problems in performance as products. Since 4,4'-dihydroxydiphenylsulfone monoether is used in a state of being dispersed in a solvent such as water, a product with a small crystal size that is easily dispersed is required. If there are lumpy particles after drying of the crystals, an additional comminuting process step is required. In order to produce products of small particle size, the comminution process sometimes becomes too complicated.

The present invention is made in consideration of the above circumstances. It is an object of the present invention to provide a process for the production of uncolored, high-purity 4,4'-dihydroxydiphenylsulfone monoethers in high yields and advantageously on an industrial scale.

The inventors of the present invention conducted intensive research to solve the above-mentioned problems. It was found that these problems can be solved by (1) if the pH is adjusted step by step, BPS can be effectively removed, (2) the alkyl halide used in the reaction remains and decomposes in the forming process step so that The product is colored, (3) the presence of metal ions such as iron in the solvent used in the production steps causes coloring and removal of ion-generating substances, and (4) the product is dried under mechanical stirring. The present invention has thus been accomplished.

The present invention relates to

(Element 1) A method for preparing a compound represented by the following formula (1):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein The process steps of adjusting the pH of the aqueous solution containing the compound of formula (I) to a predetermined value (P1), extracting with an organic solvent and separating into an organic layer and an aqueous layer and adding water or water adjusted to a fixed pH value to the separated In the organic layer, the process step (process) of separating the organic layer by adjusting the pH of the aqueous layer to a predetermined value (P2);

(Element 2) The method for producing a compound of formula (I) according to (Element 1), wherein the aqueous solution containing the compound of formula (I) is adjusted to a predetermined value (P1), extracted with an organic solvent and separated into an organic layer and an aqueous layer The process step is a process step in which the pH of the aqueous layer of the biphasic solution consisting of water and a water-immiscible organic solvent and a mixture containing the compound of formula (I) is adjusted to a predetermined value (P1) to separate the organic layer;

(Element 3) The method for producing a compound of formula (I) according to (Element 1) or (Element 2), wherein said P2 is set to a value different from said P1;

(Element 4) The method for producing a compound of formula (I) according to any one of (Element 1) to (Element 3), wherein said P2 is set to a value lower than said P1;

(Element 5) The method for producing a compound of formula (I) according to any one of (Element 1) to (Element 4), wherein the P1 is set within the range of 8.4 to 8.7 and the P2 is set at Between 8.3-8.6;

(Element 6) The method for preparing a compound of formula (I) according to any one of (Element 1) to (Element 5), wherein the aqueous solution containing the compound of formula (I) contains the compound represented by formula (II)

wherein R ^{and R} are each independently halogen, an alkyl group having 1-8 carbon atoms or an alkenyl group having 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4,

with formula (III) compound

R ³ -X (III)

Wherein ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, and X is Halogen, an aqueous solution of a reaction product obtained by reacting in a solvent in the presence of a base;

(Element 7) A method for preparing a compound of formula (I):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and R ³ is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein in the compound of formula (II)

wherein R ¹ , R ² , m and n are as defined above;

with formula (III) compound

R ³ -X (III)

wherein ^R3 is as defined above and X is halogen,

In a method of producing a compound of formula (I) by performing a reaction in a solvent in the presence of a base and then purifying the resulting reaction solution, there is provided a method wherein the compound of formula (II) and (III) is removed from the solution produced by the reaction of the compound of formula (II) and (III) III) process steps of the compound;

(Element 8) The method for producing a compound of formula (I) according to (Element 7), wherein the reaction solution is a reaction solution after completion of the reaction of compounds of formula (II) and (III);

(Element 9) The method for producing a compound of formula (I) according to (Element 7) or (Element 8), wherein immediately after the compound of formula (II) and (III) reacts in a solvent in the presence of a base, a In removing the processing step of formula (III) compound;

(Element 10) The method for producing a compound of formula (I) according to any one of (Element 7) to (Element 9), wherein adjustment of the pH of the solution including the reaction solution is provided in the production method of the compound of formula (I) and providing a process step of removing the compound of formula (III) from the reaction solution immediately before the process step of adjusting the pH of the solution including the reaction solution;

(Element 11) The method for preparing a compound of formula (I) according to any one of (Element 7) to (Element 10), wherein the process step of removing the compound of formula (II) is to distill the compound of formula (III) and the reaction solvent process steps removed together from the reaction solution;

(Element 12) The process for preparing a compound of formula (I) according to any one of (Element 7) to (Element 10), wherein the process step of removing the compound of formula (III) is to form the compound together with water and with water by distillation A process step in which the mixture of solvents of the azeotrope is removed together;

(Element 13) The method for producing a compound of formula (I) according to any one of (Element 7) to (Element 12), wherein the reaction solvent is water;

(Element 14) The method for preparing a compound of formula (I) according to any one of (Element 7) to (Element 13), wherein in the production method of the compound of formula (I), it is provided to deposit formula (I) from an organic solvent as a crystal ) compound process steps, and remove the compound of formula (III) so that the concentration of the compound in the organic solvent is 1wt% or less;

(Element 15) A method for preparing a compound of formula (I):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and R ³ is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein Be in by formula (II) compound

wherein R ¹ , R ² , m and n are as defined above,

with formula (III) compound

R ³ -X (III)

wherein ^R3 is as defined above and X is halogen,

In the process of producing a compound of formula (I) by reacting in a solvent in the presence of a base and then purifying the resulting reaction solution, in the process step of purifying a reaction mixture of a compound of formula (II) and (III) with water and an organic solvent, the formula ( III) The concentration of the compound in the organic solvent is 5 wt% or less;

(Element 16) The method for producing the compound of formula (I) according to (Element 15), wherein the concentration of the compound of formula (III) in the organic solvent is 2 wt% or less;

(Element 17) The method for producing the compound of formula (I) according to (Element 15), wherein the concentration of the compound of formula (III) in the organic solvent is 1 wt% or less;

(Element 18) A method for preparing a compound of formula (I):

Wherein R ^and R are ^each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and R ³ is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein Be in by formula (II) compound

wherein R ¹ , R ² , m and n are as defined above;

with formula (III) compound

R ³ -X (III)

wherein ^R3 is as defined above and X is halogen,

In an aqueous solvent of 0.3-1.5 parts by weight relative to 1 part by weight of a compound of formula (II), react in the presence of a base of 1.5-3 mol relative to 1 mol of a compound of formula (II) and remove the compound of formula (III) by distillation to produce In the method for the compound of formula (I), the compound of formula (III) is heated and distilled off, and then further water is added to remove the compound of formula (III) by distillation;

(Element 19) The method for producing the compound of formula (I) according to (Element 18), wherein the amount of water added is 0.03-0.1 parts by weight relative to 1 part by weight of the compound of formula (II);

(Element 20) The method for producing the compound of formula (I) according to (Element 18), wherein the amount of water added is 0.04-0.08 parts by weight relative to 1 part by weight of the compound of formula (II);

(Element 21) The method for producing a compound of formula (I) according to (Element 18), wherein water is added separately two or more times;

(Element 22) The method for producing the compound of formula (I) according to (Element 21), wherein the amount of water added at the beginning is 0.03-0.1 parts by weight relative to 1 part by weight of the compound of formula (II);

(Element 23) The method for producing the compound of formula (I) according to (Element 21), wherein the amount of water added is 0.04-0.08 parts by weight relative to 1 part by weight of the compound of formula (II);

(Element 24) A method for preparing a compound of formula (I):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and R ³ is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein In the method for producing the compound of formula (I) by performing the reaction in a solvent to obtain the compound of formula (I), a solvent containing an iron component of 0.05 ppm or less is used as the solvent;

(Element 25) The method for producing a compound of formula (I) according to (Element 24), wherein the reaction solvent is a reaction solvent containing water;

(Element 26) A method for preparing a compound of formula (I):

Wherein R ^and R are ^each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein Water containing an iron component of 0.05 ppm or less is used as water in the purification step of removing compounds other than the compound of formula (I) from a mixture containing the compound of formula (I);

(Element 27) A method for preparing a compound of formula (I):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein in A container with a corrosion-resistant layer on the inner wall is used in the reaction step of producing the compound of formula (I);

(Element 28) A method for preparing a compound of formula (I):

Wherein R ^and R are ^each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein in A container having a corrosion-resistant layer on the inner wall is used in a purification step for removing compounds other than compounds of formula (I) from a mixture containing the compound of formula (I);

(Element 29) The method for producing a compound of formula (I) according to (Element 24) or (Element 25), wherein the corrosion-resistant layer is a layer composed of at least one material selected from titanium, glass and fluororesin;

(Element 30) The method for preparing a compound of formula (I) according to any one of (Element 24) to (Element 29), wherein the reaction step for producing the compound of formula (I) is a compound represented by formula (II)

Wherein R ^and R are ^each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4;

with formula (III) compound

R ³ -X (III)

wherein ^R3 is as defined above and X is halogen,

The process step of carrying out the reaction in the presence of a base in a solvent;

(Element 31) A method for preparing a compound of formula (I):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein in Adding a chelating agent in the purification step of removing compounds other than the compound of formula (I) from a mixture containing the compound of formula (I);

(Element 32) A method for preparing a compound of formula (I):

Wherein R ^{and R} are each independently halogen, an alkyl group with 1-8 carbon atoms or an alkenyl group with 2-8 carbon atoms; m and n are each independently an integer of 0 or 1-4; and R ³ is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group, wherein In the process of producing a compound of formula (I) with a drying process step, drying the product under mechanical stirring in the drying process step;

(Element 33) The method for producing the compound of formula (I) according to (Element 32), wherein the product is heated and dried under reduced pressure under mechanical stirring;

(Element 34) The method for producing a compound of formula (I) according to (Element 32) or (Element 33), wherein the compound of formula (I) is in a temperature having a melting point lower than the melting point of the compound of formula (I) before drying the state of performance;

(Element 35) The method for producing a compound of formula (I) according to any one of (Element 32) to (Element 34), wherein the compound of formula (I) is in a state of forming a molecular compound with a solvent before drying;

(Element 36) The method for producing a compound of formula (I) according to (Element 35), wherein the solvent is an organic solvent;

(Element 37) The method for preparing a compound of formula (I) according to (Element 36), wherein the organic solvent is an aromatic hydrocarbon; and

(Element 38) The method for preparing a compound of formula (I) according to any one of claims 1-37, wherein the compound of formula (I) is a compound of formula (IV):

Wherein ^R is an alkyl group having 1-8 carbon atoms, an alkenyl group having 2-8 carbon atoms, a cycloalkyl group having 3-8 carbon atoms or an optionally substituted aralkyl group.

The invention is described in more detail below.

The present invention mainly consists of (element 1), (element 7), (element 15), (element 18), (element 24), (element 26), (element 27), (element 28), (element 31) and ( Element 32) Composition. They each relate to a process for producing a compound of formula (I).

In formula (I), R ^and R are ^each independently halogen such as fluorine, chlorine, bromine or iodine; alkyl groups with 1-8 carbon atoms such as methyl, ethyl, n-propyl, isopropyl , n-butyl or tert-butyl; or alkenyl having 2-8 carbon atoms such as propenyl, isopropenyl or butenyl. m and n are each independently 0 or an integer of 1-4. When m and n are numbers of 1 or more, the substitution position is not limited.

In formula (I), R ³ is an alkyl group with 1-8 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl or tert-butyl; Alkenyl such as propenyl, isopropenyl or butenyl; cycloalkyl having 3-8 carbon atoms such as cyclopropyl, cyclopentyl or cyclohexyl; or optionally substituted aralkyl such as benzyl, 4-chlorobenzyl or 2-phenylethyl. Among them, preferred compounds of formula (I) are those wherein R is an alkyl group having 2-4 carbon atoms, such as ethyl, n-propyl, isopropyl, n-butyl or tert-butyl, or optionally substituted Aralkyl such as benzyl compounds. Compounds wherein ^R3 is isopropyl are particularly preferred. There is no particular limitation on the substitution positions of the hydroxyl group (OH group) and the OR ³ group. However, it is preferred that they are each in the para position (4 or 4' position) to the sulfonyl group. This compound can be advantageously used to produce compounds of formula (IV) in which these groups are each in the 4 or 4' position.

Examples of compounds represented by formula (IV) include 4-methoxy-4'-hydroxyl diphenyl sulfone, 4-ethoxy-4'-hydroxyl diphenyl sulfone, 4-n-propoxy-4'- Hydroxydiphenylsulfone, 4-isopropoxy-4′-hydroxydiphenylsulfone, 4-n-butoxy-4′-hydroxydiphenylsulfone, 4-sec-butoxy-4′-hydroxydiphenylsulfone Phenylsulfone and 4-tert-butoxy-4'-hydroxydiphenylsulfone. Of these, 4-isopropoxy-4'-hydroxydiphenylsulfone is particularly preferred.

The production method of the present invention is not only applicable to the compound of formula (I), but also applicable to the compound shown in formula (V):

Wherein R ¹ , R ² , m and n are as defined above, and Q is a group shown in formula (VI):

Wherein X and Y are each independently a saturated or unsaturated, optionally substituted hydrocarbon with 1-12 carbon atoms, a saturated or unsaturated hydrocarbon with 1-12 carbon atoms and an ether bond, formula (VII) Groups shown:

Wherein ^R is methylene or ethylene, or a group shown in formula (VIII):

Wherein R ⁹ is hydrogen or an alkyl group with 1-4 carbon atoms;

R ⁴ -R ⁷ are each independently halogen, an alkyl group having 1-8 carbon atoms or an alkenyl group having 2-8 carbon atoms; p, q, r and t are each independently 0 or 1 to 4 and a is an integer of 0 or 1 to 10. Especially preferred are the production methods associated with (Element 11), (Element 13) and (Element 16).

Examples of X and Y in formula (VI) are each independently optionally substituted saturated hydrocarbons having 1 to 12 carbon atoms, such as methylene, ethylene, trimethylene, tetramethylene, penta Methylene, Hexamethylene, Heptamethylene, Octamethylene, Nonamethylene, Decamethylene, Undecamethylene, Dodecamethylene, Methylmethylene, Dimethyl Methylene, methylethylene, methyleneethylene, ethylethylene, 1,2-dimethylethylene, 1-methyltrimethylene, 1-methyltetramethylene , 1,3-Dimethyltrimethylene, 1-ethyl-4-methyl-tetramethylene, 2-hydroxytrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy- 2-Ethyltrimethylene, 2-Hydroxy-2-propyltrimethylene, 2-Hydroxy-2-isopropyltrimethylene and 2-Hydroxy-2-butyltrimethylene; with 1-12 Optionally substituted unsaturated hydrocarbons of carbon atoms, such as vinylene, propenylene, 2-butenylene, ethynylene, 2-butynylene and 1-vinylethylene; and having 1-12 Saturated or unsaturated hydrocarbons with carbon atoms and ether bonds, such as ethyleneoxyethylene, tetramethyleneoxytetramethylene, ethyleneoxyethyleneoxyethylene, ethylene oxymethyleneoxyethylene, and 1,3-dioxane-5,5-bismethylene.

Examples of R in formula ( ^VII ) include methylene and ethylene, and examples of R in formula (VIII) include hydrogen and ^alkyl groups with 1-4 carbon atoms, such as methyl, ethyl , n-propyl, isopropyl, n-butyl and tert-butyl.

Examples of R ⁴ -R ⁷ are each independently halogen such as fluorine, chlorine and bromine; alkyl having 1-8 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl and tert- butyl; and alkenyl having 2 to 8 carbon atoms, such as vinyl, propenyl, isopropenyl and butenyl.

The following are examples of compounds of formula (V):

1) wherein X and/or Y in the formula are optionally substituted saturated hydrocarbon compounds having 1-12 carbon atoms;

4-[4-(4-hydroxyphenylsulfonyl)phenoxy-4-butoxy]-4'-[4-(4-hydroxyphenylsulfonyl)phenoxy-3-propoxy] Diphenylsulfone, 4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy-2-ethoxy]diphenylsulfone, 4,4'-bis[4-(4- Hydroxyphenylsulfonyl)phenoxy-3-propoxy]diphenylsulfone, 4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy-4-butoxy]di Phenylsulfone, 4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy-5-pentyloxy]diphenylsulfone, 4,4'-bis[4-(4-hydroxy Phenylsulfonyl)phenoxy-6-hexyloxy]diphenylsulfone, 4-[4-(4-hydroxyphenylsulfonyl)phenoxy-4-butoxy]-4'-[4 -(4-hydroxyphenylsulfonyl)phenoxy-2-ethoxy]diphenylsulfone, 4-[4-(4-hydroxyphenylsulfonyl)phenoxy-3-propoxy]- 4'-[4-(4-hydroxyphenylsulfonyl)phenoxy-2-ethoxy]diphenylsulfone, 4,4'-bis[4-[4-(2-hydroxyphenylsulfonyl) )phenoxy]butoxy]diphenylsulfone, 4,4'-bis[4-[2-(4-hydroxyphenylsulfonyl)phenoxy]butoxy]diphenylsulfone, 1, 1-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]methane, 1,2-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]ethane, 1,3-bis [4-(4-Hydroxyphenylsulfonyl)phenoxy]propane, 1,4-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]butane, 1,5-bis[4- (4-hydroxyphenylsulfonyl)phenoxy]pentane and 1,6-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]hexane.

2) wherein X and/or Y in the formula are optionally substituted unsaturated hydrocarbon compounds having 1-12 carbon atoms;

1,2-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]ethylene, 4,4'-bis[4-[4-(4-hydroxyphenylsulfonyl)phenoxy]-2 -trans-butenyloxy]diphenylsulfone, 4-[4-[4-(4-hydroxyphenylsulfonyl)phenoxy]-2-trans-butenyloxy]-4 '-[4-(4-hydroxyphenylsulfonyl)phenoxy-4-butoxy]diphenylsulfone, 4-[4-(4-hydroxyphenylsulfonyl)phenoxy]-2- trans-butenyloxy]-4'-[4-(4-hydroxyphenylsulfonyl)phenoxy-3-propoxy]diphenylsulfone, 4-[4-[4-(4 -Hydroxyphenylsulfonyl)phenoxy]-2-trans-butenyloxy]-4'-[4-(4-hydroxyphenylsulfonyl)phenoxy-2-ethoxy]di Phenylsulfone, 1,4-bis[4-[4-[4-(4-hydroxyphenylsulfonyl)phenoxy-2-trans-butenyloxy]benzenesulfonyl]phenoxy] -cis-2-butene and 1,4-bis[4-[4-[4-(4-hydroxyphenylsulfonyl)phenoxy-2-trans-butenyloxy]benzenesulfonyl ]phenoxy]-trans-2-butene.

3) wherein X and/or Y in the formula are saturated or unsaturated hydrocarbon compounds having 1-12 carbon atoms and ether linkages;

4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]dibutyl ether, 2,2'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]diethyl ether , 4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy-2-ethyleneoxyethoxy]diphenyl sulfone, 2,2'-bis[4-[4 -[4-(4-Hydroxyphenylsulfonyl)phenoxy-2-idene-ethyloxyethoxy]benzenesulfonyl]phenoxy]diethyl ether, 2,4'-bis[2-( 4-Hydroxyphenylsulfonyl)phenoxy-2-ethyleneoxyethoxy]diphenylsulfone, 2,4'-bis[4-(2-hydroxyphenylsulfonyl)phenoxy- 2-Ethyleneoxyethoxy]diphenylsulfone, 4,4'-bis[3,5-dimethyl-4-(3,5-dimethyl-4-hydroxyphenylsulfonyl) Phenoxy-2-ethyleneoxyethoxy]diphenylsulfone and 4,4′-bis[3-allyl-4-(3-allyl-4-hydroxyphenylsulfonyl) Phenoxy-2-ethyleneoxyethoxy]diphenylsulfone.

4) wherein X and/or Y in the formula are compounds represented by the formula (VII);

α,α'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]-p-xylene, α,α'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]- m-xylene, α,α′-bis[4-(4-hydroxyphenylsulfonyl)phenoxy]-o-xylene, α,α′-bis[4-[4-[4-(4-hydroxy Phenylsulfonyl)phenyl-1,4-phenylenebismethyleneoxy]benzenesulfonyl]phenoxy]-p-xylene, α,α′-bis[4-[4-[4- (4-Hydroxyphenylsulfonyl)phenyl-1,3-phenylenebismethyleneoxy]benzenesulfonyl]phenoxy]-m-xylene, α,α′-bis[4-[4 -[4-(4-Hydroxyphenylsulfonyl)phenyl-1,2-phenylene bis-methyleneoxy]benzenesulfonyl]phenoxy]-o-xylene, 4,4'-bis[ 4-(4-Hydroxyphenylsulfonyl)phenyl-1,4-phenylenebismethyleneoxy]diphenylsulfone, 4,4'-bis[4-(4-hydroxyphenylsulfonyl) ) phenyl-1,3-phenylene bis-methyleneoxy] diphenylsulfone, 4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenyl-1,2-phenylene Bismethyleneoxy]diphenylsulfone, 4,4'-bis[3,5-dimethyl-4-(3,5-dimethyl-4-hydroxyphenylsulfonyl)phenyl- 1,4-phenylenebismethyleneoxy]diphenylsulfone, 4,4'-bis[3,5-dimethyl-4-(3,5-dimethyl-4-hydroxyphenyl Sulfonyl)phenyl-1,3-phenylenebismethyleneoxy]diphenylsulfone, 4,4'-bis[3,5-dimethyl-4-(3,5-dimethyl -4-Hydroxyphenylsulfonyl)phenyl-1,2-phenylene bis-methyleneoxy]diphenylsulfone, 4,4'-bis[3-allyl-4-(3-ene Propyl-4-hydroxyphenylsulfonyl)-1,4-phenylene bis-methyleneoxy]diphenylsulfone, 4,4'-bis[3-allyl-4-(3-ene Propyl-4-hydroxyphenylsulfonyl)-1,3-phenylenebismethyleneoxy]diphenylsulfone and 4,4′-bis[3-allyl-4-(3-ene Propyl-4-hydroxyphenylsulfonyl)-1,2-phenylenebismethyleneoxy]diphenylsulfone.

5) wherein X and/or Y in the formula are compounds represented by the formula (VIII);

4,4'-bis[4-(4-hydroxyphenylsulfonyl)phenoxy-2-hydroxypropoxy]diphenylsulfone and 1,3-bis[4-[4-[4-(4 -hydroxyphenylsulfonyl)phenoxy-2-hydroxypropoxy]benzenesulfonyl]phenoxy]-2-hydroxypropane.

Among these compounds, preferred are those wherein a is 0 or an integer of _{1 to 3, and X and/or Y are -CH2CH2-O-CH2CH2- or -CHCH = CHCH2-} .

The compound of formula (V) can be prepared according to the method for producing the compound of formula (I) described later, by using the compound shown in formula (IX) instead of the compound of formula (III):

A ¹ -XA ² or A ³ -YA ⁴ (IX)

wherein A ¹ -A ⁴ are each independently halogen. The product is a single compound or a mixture of several compounds. The present invention is applicable to the separation or purification of these compounds from starting materials and by-products.

There is no particular limitation on the method of synthesizing the compound represented by formula (I) (hereinafter referred to as compound (I)), except for inventions related to (Element 15) and (Element 18). The method of allowing the compound represented by formula (II) (hereinafter referred to as compound (II)) to react with the compound represented by formula (III) (hereinafter referred to as compound (III)) in a solvent in the presence of a base is exemplified as the most preferable.

In formula (III), X is halogen such as chlorine, bromine or iodine. Examples of compounds of formula (III) include alkyl halides such as methyl iodide, ethyl iodide, ethyl bromide, n-propyl iodide, n-propyl bromide, n-propyl chloride, isopropyl iodide, isopropyl bromide, Isopropyl chloride, n-butyl iodide, n-butyl bromide, sec-butyl iodide, sec-butyl bromide, tert-butyl iodide, tert-butyl bromide, n-pentyl iodide, n-pentyl bromide, n-hexyl iodide and n-hexyl bromide; alkenyl halides such as allyl chloride, allyl bromide, allyl iodide, butenyl chloride and butenyl bromide; cycloalkyl halides such as cyclopropyl iodide, cyclopropyl bromide, cyclo Propyl chloride, cyclopentyl iodide, cyclopentyl bromide, cyclopentyl chloride, cyclohexyl iodide, cyclohexyl bromide, and cyclohexyl chloride; and aralkyl halides such as benzyl iodide, benzyl bromide, benzyl chloride, 4-chlorobenzyl iodide, 4-methylbenzyl bromide, 3-chlorobenzyl chloride, (1-phenyl)ethyl iodide, (1-phenyl)ethyl bromide, 2-phenylethyl bromide, 2-Phenylethyl chloride and 3-phenylpropyl bromide.

Among them, preferred compounds of formula (III) are those wherein X is bromine. Particular preference is given to using isopropyl bromide. The amount of compound (III) used is generally between 1-3 mol, preferably between 1-1.5 mol, relative to 1 mol of compound (II).

Examples of the base used in the reaction include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; alkali metal carbonates such as calcium carbonate; and Organic amines such as triethylamine, pyridine and diazabicyclo[5.4.0]undec-7-ene. Among these, bases including alkali metal hydroxides such as sodium hydroxide are particularly preferred. The amount of base used is usually between 1-5 mol, preferably between 1.5-3 mol, relative to 1 mol of compound (II).

Examples of solvents used include water; amides such as N,N-dimethylformamide and N,N-dimethylacetamide; alcohols such as methanol, ethanol and propanol; and two-phase mixture solvents such as water-toluene, Water-Xylene and Water-Benzene. The amount of the solvent used is usually in the range of 0.1 to 10 parts by weight relative to 1 part by weight of compound (II).

The reaction method is, for example, by adding compound (III) to a solution of alkali metal salt of compound (II). There is no particular limitation on how to add compound (III). Examples are methods of continuously dropping a quantitative amount of compound (2) into a reaction solution and adding compound (III) little by little over several times. The reaction is usually carried out at a temperature between room temperature and the boiling point of the solvent, preferably between 45-80°C, and is usually completed within about 1-25 hours.

The method for producing the compound of formula (I) in the present invention is a general term for all process steps from raw materials to the completion of the product, covering the reaction steps of allowing the starting materials to react to obtain a reaction mixture containing the compound of formula (I), such as letting A process step of reacting compound (II) with compound (III), and a purification step such as separation of substances and impurities; a process step of isolating compound (I) after completion of the purification step, such as crystallization, distillation, filtration and recrystallization; and Process steps especially required for industrial production, such as drying and solvent recovery. Examples are combinations of a series of process steps of pretreatment, reaction, purification, crystallization, filtration, drying and solvent recovery, and combinations of two or more of each process step.

The reaction mixture thus obtained contains compound (I) and impurities such as unreacted compound (II), unreacted compound (III) and 4,4'-dihydroxydiphenylsulfone diether by-product. It is therefore necessary to separate these impurities from the reaction mixture, that is, to purify the reaction mixture, in order to produce a high-purity target compound.

When the reaction mixture of 4,4'-dihydroxydiphenyl sulfone (hereinafter referred to as BPS) and compound (III) is purified to separate the target compound, i.e. the compound shown in formula (V) (hereinafter referred to as compound (V)), The production method of the present invention is described in detail using examples.

In order to react BPS and compound (III) in the presence of a base, for example, a BPS salt formed from BPS and a base is reacted with compound (III). The solubility of BPS salt in non-polar organic solvents is low, so the reaction is usually carried out in polar solvents, water or a mixed solvent of water and organic solvents. BPS has two positions to form a salt with a base in one molecule. The problem is how to control the generation of 4,4'-dihydroxydiphenylsulfone diether (hereinafter sometimes referred to as diether) by-product in this reaction.

For example, in view of the solubility of the salt of compound (V) and base (hereinafter referred to as compound (V) salt) in water is lower than the solubility of the di-salt compound in water, there is a compound (III) and di-salt compound in saturated or A method in which the compound (V) salt is deposited by reacting in an almost saturated aqueous solution so as to move out of the reaction system as crystals.

Another example is to carry out the reaction in a biphasic system of water and a water-immiscible organic solvent (which dissolves compound (V) to some extent), the pH being controlled to limit the disalt and compound (V) salt. Formed, and the produced compound (V) is dissolved in the organic solvent to be removed from the system.

In either method, after the reaction is complete, the reaction mixture contains impurities of BPS, diether, and the like. If such impurities are contained, it is difficult to isolate the high-purity target compound in crystal form only by operations such as recrystallization because the structure of the impurities is similar to that of the target compound. One method is used to separate impurities by pH adjustment, because BPS, compound (V) and diether have differences in acidity.

Purification of the reaction mixture to isolate the target compound is performed, for example, according to the procedure described below:

(a) First, unreacted compound (III) is removed.

The reaction solution usually contains unreacted compound (III). Compound (III) is generally unstable in water, especially in alkaline aqueous solution, and is more unstable and easily decomposed when heated. As described above, when water is used as a reaction solvent and an alkali is used as a base, compound (III) needs to be used in excess because it is easily decomposed in the reaction step. Compound (III) decomposes to generate acid if present in post-treatment process steps such as purification after the end of the reaction. The acid reacts with the base to lower the pH of the reaction solution.

The drop in pH is local and its variation is small. However, precise pH adjustment is especially required (described below) in order to accurately separate target compounds into the organic layer and impurities into the alkaline aqueous layer. Non-uniform pH or a pH different from the predetermined value will lead to difficulties in the complete separation of the target compound from the raw materials and by-products.

In this reaction, the reaction solution is sometimes colored and the product, compound (V), is also colored in the process step of purifying the reaction solution after the completion of the reaction. Once the product is colored, the problem is that decolorization is difficult.

The present inventors studied the cause of coloring in detail. As a result, it is considered that the reason for the coloring of the reaction solution in the purification step is because heavy metal ions such as iron ions contained in the industrial water used as the reaction solvent and water used in the purification step or dissolved out from the SUS reaction vessel have a phenolic hydroxyl group. Compounds such as compound (V) form a chelate, which is responsible for coloring. It is also considered that the chelate causing coloring is easily formed because a local decrease in the pH of the reaction solution creates a pH region in which the compound having a phenolic group can form a chelate with heavy metal ions. It is therefore necessary to precisely and uniformly control the pH during the purification step in order to effectively prevent the formation of chelates and produce uncolored products.

By providing a process step of removing unreacted compound (III) contained in the reaction solution in the process step of purifying the reaction solution after the completion of the reaction, the present invention makes it possible to prevent changes in the pH of the reaction solution due to decomposition of the compound (III) value to precisely adjust the pH.

Compound (III) can be removed after completion of the reaction and before isolation of the target compound. In the present invention, it is advantageous to remove compound (III) after the end of the reaction and before the pH adjustment of the aqueous layer in order to adjust the pH accurately and control the pH variation to the minimum. It is more favorable to remove unreacted compound (III) after the reaction is completed and before the diether is extracted with an organic solvent for removal. In other words, it is preferable to provide a process step of removing compound (III) immediately after the reaction step.

There is no particular limitation on the method of removing compound (III). Examples include (1) after the reaction is completed, the reaction solution is heated to evaporate and remove the compound (III); (2) after the reaction is completed, an extraction solvent, such as benzene or toluene, is added to the reaction solution to extract and remove the compound (III); ).

Among them, method (1) is simpler in the present invention. In the evaporative removal operation in the method (1), it is preferable to distill off the compound (III) together with the solvent used for the reaction. Especially when water is used as a reaction solvent, it is advantageous to add a solvent that forms an azeotrope with water, such as toluene or benzene, and then distill compound (III) out together with the mixed solvent, because compound (III) can Recycled at low temperature with minimal decomposition. Method (1) can be performed at atmospheric pressure or under reduced pressure. If carried out under reduced pressure, unreacted compound (III) can be removed by evaporation at a lower temperature, and thus the change in pH due to the decomposition of compound (III) can be controlled.

Compound (III) removed from the reaction solution can be recovered or obtained by other means for reuse.

Reaction is carried out in the presence of a base of 1.5-3 mol relative to 1 mol of compound (II) in compound (II) such as BPS and compound (III) in an aqueous solvent of 0.3-1.5 parts by weight relative to 1 part by weight of compound (II) And in the method for producing the compound (I) with the process step of removing the compound (III) after carrying out distillation of the compound (III) thereafter, if the compound (III) is distilled out by heating and further adding water to remove the compound (III by distillation) ), the compound can be efficiently recovered and the production of impurities such as diethers can be controlled.

It is advantageous to add water individually over several times. In addition, the amount of water added at the beginning is in the range of 0.03-0.1 part by weight, more preferably 0.04-0.08 part by weight, with respect to 1 part by weight of compound (II). It is advantageous to control the amount of water added at the beginning in order to facilitate sufficient recovery of compound (III). If it is less than 0.03 parts by weight, compound (III) cannot be sufficiently distilled out. If it exceeds 0.1 parts by weight, more impurities such as diether are produced. The amount of water added at the second and subsequent times may be the same as that at the beginning, or more if the compound (III) remains in a small amount.

The smaller the amount of compound (III) remaining in the reaction solution after compound (III) is distilled off, the more preferable. For larger reaction scales, it is more difficult to completely remove this compound by distillation. Compound (III) remaining in the reaction solution after distillation may, for example, contain an organic solvent used in the process step for crystallization of compound (I) (compound (V)) from an organic solvent through subsequent process steps (post processes) middle. After compound (I) is filtered, the organic solvent used for crystallization is often recovered for reuse. Reuse of a solvent containing a large amount of compound (III), as described above, causes problems such as decomposition of compound (III) to color compound (I) in various process steps. Therefore, it is necessary to reduce the amount of compound (III) in the organic solvent. It is generally preferred to control to 1 wt% or less. It is advantageous to distill off compound (III) so that the content of compound (III) in the organic solvent used in the crystallization step is 1 wt% or less.

(b) Next, a water-immiscible solvent and, if necessary, water and/or base (aqueous solution) are added to the reaction mixture to form a two-phase solution of an organic layer and an aqueous layer. When a polar solvent is used for the reaction, it is preferred to carry out the operation after the polar solvent is recovered or removed. It is also advantageous to adjust the pH to 8 or above in order to completely separate the diether from the compound (V) salt. There are no particular restrictions on the water-immiscible solvents if they are organic solvents immiscible with water. Preference is given to using aromatic hydrocarbons such as toluene, xylene and benzene. The separation operation separates the diether without phenolic hydroxyl group into the organic layer and the target compound into the aqueous layer.

In order to prevent the crystallization of the target compound, impurities, etc., the separation operation is advantageously carried out at a temperature higher than the crystallization temperature, usually in the temperature range of 70-90°C. The amount of water-immiscible organic solvent used is usually in the range of 0.5-5 ml relative to 1 g of BPS used as starting material. Both the produced compound (V) and unreacted BPS were soluble in alkaline aqueous solution, but the diether was insoluble. Without using a water-immiscible organic solvent, the diether can be removed by adjusting the pH of the resulting reaction mixture to 8 after the removal of the organic solvent and the like (or after the end of the reaction if water is used as the reaction solvent). or above 8 and filter off the deposited diether.

(c) Then, the aqueous layer containing the target compound is separated. A water-immiscible organic solvent and, if necessary, water are added to the resulting aqueous layer to form a biphasic solution of organic and aqueous layers. The pH of the aqueous layer was adjusted to a predetermined value (P1). Adjusting the pH to a predetermined value (P1) will separate the target compound into the organic layer, while impurities including BPS will be separated into the alkaline aqueous layer. The pH is usually adjusted by adding an acid or base to the aqueous layer. In this case, after adjusting the pH of the aqueous layer, a water-immiscible organic solvent may be added to extract the target compound.

Examples of usable acids include hydrochloric acid, sulfuric acid and nitric acid. Sodium hydroxide and potassium hydroxide are exemplified as usable bases. The base can be added in the form of an aqueous solution when used. In order to prevent a sharp pH change and to adjust the pH accurately, it is preferable to add an acid or a base in a little amount while stirring the whole mixture well. The predetermined value (P1) of pH is usually in the range of 8-9, preferably 8.3-8.7. In this case, in order to prevent crystallization of the target compound and impurities, it is advantageous to add a water-immiscible organic solvent and water (if necessary) to the reaction solution and keep the temperature above the crystallization temperature, usually at 70-90°C Simultaneous separation within the range.

(d) Further, water and, if necessary, a water-immiscible organic solvent are added to the organic layer obtained after removal of the water layer to form a two-phase solution again, and the pH of the water layer is adjusted to a predetermined value (P2). Especially when the reaction mixture has a high concentration, a third layer in which the target compound is not completely separated from BPS and other substances will be formed near the interface between the organic layer and the aqueous layer. In this case, it is necessary to remove the completely separated aqueous layer and adjust the pH of the remaining organic layer and the third layer in order to completely separate the BPS from the target compound.

In the prior art, water and a water-immiscible organic solvent are added to the reaction product containing the target compound to form a two-phase solution, the pH of the aqueous layer is adjusted to a predetermined value to separate the organic layer, and the target compound is obtained from the organic layer. compound. However, particularly when purifying a high-concentration reaction mixture, for example, when a reaction mixture obtained from a reaction of a high-concentration raw material or a reaction mixture containing a high-concentration inorganic salt is purified without too much dilution, it is difficult to A single pH adjustment separates target compounds from impurities.

The inventors of the present invention have investigated the cause of the above difficulties. As a result, the following factors are considered to be the difficulty in the complete separation of the target compound from impurities:

(1) The difference in acidity between the compound (V) and the phenolic hydroxyl group of BPS is small. Therefore, it is impossible to completely separate the target compound from BPS and other substances without precise pH adjustment.

(2) Both the target compound and BPS are less soluble in water and water-immiscible solvents. Therefore, when a water-immiscible solvent is added to a mixture of these to form a two-phase solution, particularly when a solution of the mixture is used at a high concentration, the compound (V) wherein compound (V) is formed near the interface between the aqueous layer and the organic layer A third intermediate layer that is mixed with BPS without separation. So, their separation is not enough. The ratio of this layer in the whole solution tends to become larger as the concentration of the reaction product becomes higher.

(3) Due to the salting-out effect of a large amount of inorganic salts produced from the reaction of compound (III) and BPS, the BPS salt will not be completely soluble in the water layer, nor can it be dissolved in the organic layer, so that the compound (V ) intervenes to form the third layer.

(4) On the other hand, when the target compound is produced on an industrial scale, a considerable amount of water and a water-immiscible organic solvent cannot be added to the reaction solution because of the working efficiency and capacity of the reaction and processing vessels.

(5) Therefore, it is often the case that when a series of operations of adjusting the pH of the aqueous layer to be treated to a predetermined value and separating the organic layer are performed only once, it is difficult to completely remove the target compound (compound (V)) Separated from BPS.

Based on the above facts, in the present invention, a series of operations consisting of pH adjustment of the aqueous layer of the two-phase solution and separation of the organic layer can be repeated several times in order to produce a high-purity target compound with high yield.

The present invention provides a method for producing 4,4'-dihydroxydiphenylsulfone monoether, wherein a high-purity target compound is efficiently separated from a mixture even if the mixture contains the target compound and high concentrations of impurities.

When purifying the reaction product obtained from the reaction of BPS with a compound of formula (III) in a solvent in the presence of a base, the only requirements are the pH adjustment of the aqueous layer of the two-phase solution and the separation of the organic layer. These operations are not increased at all. The current production line needs to be changed.

Therefore, according to the purification method of the present invention, extremely high-purity 4,4'-dihydroxydiphenylsulfone monoether can be advantageously produced industrially.

The second pH adjustment can be performed by operations similar to the first one. Adjusting the pH of the aqueous layer to a predetermined value (P2) will allow impurities contained in the organic layer to be removed into the aqueous layer. The pH (P2) can be set to the same value as P1. However, it is preferable to set P2 slightly different from the pH value of the first adjustment in order to completely separate the target compound from the BPS. Setting P2 to a value lower than P1 is preferable. For example, P1 is set in the range of 8.4-8.7 and P2 in the range of 8.3-8.6. The series of operations of pH adjustment of the aqueous layer of the biphasic solution and separation of the organic layer can be further repeated if necessary.

As described above, if a series of operations of adjusting the pH of the aqueous layer to a predetermined value (P1 and P2) and separating the organic layer in the process step of purifying the reaction solution are repeated two or more times, it is possible to separate from the reaction mixture. Produce extremely high-purity 4,4'-dihydroxydiphenylsulfone monoether.

After adjusting the pH of the reaction solution produced from the reaction of compound (II) and compound (III) in a solvent in the presence of a base, water and an organic solvent of impurities other than compound (I) are removed from the reaction solution as described above In the process step of purification, it is preferable to set the concentration of the compound of formula (III) in the organic solvent to be 5 wt% or lower, more preferably 2 wt% or lower, and further preferably 1 wt% or lower. The organic solvent used in the purification step (as described above) is often an organic solvent, such as the solvent used in the crystallization step and recovered for reuse. In this case, the solvent may contain the compounds involved in the reaction. Among them, compound (III) is easily decomposed when brought into contact with water, alkali or the like. The use of an organic solvent containing such a compound for the purification step causes various problems including coloring of the compound (I). It is necessary to reduce the content of such impurities as much as possible. In order to reduce the amount of compound (III) contained in the organic solvent used in the purification step, a new organic solvent can be used instead of the recovered organic solvent reused. Recovered solvents after precision distillation can also be used. However, for efficient production as a whole, it is preferable to distill unreacted compound (III) out of the system as much as possible in the process step of distilling off compound (III) so that none of the compound (III) remains.

(e) Finally, after the final pH adjustment, the organic layer is separated from the biphasic solution, washed with water if necessary, cooled to deposit crystals. The crystals were isolated by filtration, washed with water and dried to obtain the title compound.

Compound (I) often forms a molecular compound especially with a crystallization solvent in the crystallization step to precipitate the compound as a crystal due to its structure and electronic properties. If compound (I) forming a molecular compound with a crystallization solvent or the like is filtered out and heated and dried under reduced pressure while standing still, the compound simultaneously melts while disintegrating the crystal form as the molecular compound, and forms an amorphous Agglomerated particles, leaving the surrounding crystals in a state of keeping the solvent inside, which breaks the bond formed with the compound (I) and evaporates out in the middle of the process step. There is no problem if the compound melts at a temperature higher than the melting point of compound (I), because compound (I) itself does not crystallize even if solvent molecules are released. In the case of melting below the melting point of compound (I), compound (I) crystallization and solvent evaporation occur after the molecular compound is melted. Therefore, it is often the case that a part of the solvent is not completely evaporated and contained inside the bulk particles. It is very difficult to crush the lumpy particles unless very strong force is applied from the outside. The solvent contained inside cannot be completely removed.

Therefore, the present invention is characterized by drying under mechanical agitation. It is particularly advantageous to heat dry under reduced pressure with mechanical stirring.

Examples of solvents that form molecular compounds with compound (I) include water; alcohols such as methanol, ethanol, n-propanol, isopropanol and 1,2-butanediol; ketones such as acetone, methyl ethyl ketone and acetylacetone Nitriles such as acetonitrile and benzonitrile; Ethers such as diethyl ether, dibutyl ether, tetrahydrofuran and dioxane; Esters such as methyl acetate, ethyl acetate and butyl acetate; Amides such as N,N-dimethylformamide and N,N-Dimethylacetamide; halogenated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, and chlorobenzene; aromatic hydrocarbons such as dimethylsulfoxide, benzene, toluene, and xylene; and aliphatic hydrocarbons Such as hexane, cyclohexane and decahydronaphthalene. In particular, molecular compounds formed with aromatic hydrocarbons such as benzene or toluene are preferably dried according to the process of the invention, since the compounds tend to melt during this process step.

There is no particular limitation on the ratio of compound (I) and solvent to form the molecular compound. Specifically, the ratio is in the range of 0.1 to 10 mol of solvent relative to 1 mol of compound (I).

In the present invention, "mechanical stirring" refers to stirring molecular compounds with a stirring device. Examples of agitating devices include those having agitating blades such as inclined paddles, flat paddles, propeller blades, anchor paddles, faudler paddles, turbine blades, bull margin blades, max blend blades, full segment blades, ribbon blades, supermixing blades or inter mig blades; and those having rotating disks, such as disks, notched disks or screws.

The vacuum stirring device with stirring device may be of batch type or continuous type. Examples include Paddle Dryer (manufactured by Nippon Kansoki Co., Ltd), Multifin Processor (manufactured by NaraKikai Seisakusho Co., Ltd), Plow Share Mixer (manufactured by Taiheiyo Kiko Co., Ltd), and Inklandent Dryer (manufactured by Tukishima Kikai Co., Ltd) .

The speed of stirring depends on the type of stirring device used and other conditions. About 1-10 rpm is usually satisfactory.

The heating temperature varies depending on the type of solvent to be evaporated. For example when toluene is used, it is preferably in the range from room temperature to 100°C, particularly advantageously in the range from 50-90°C.

Drying under reduced pressure is usually performed at 200 mmHg or lower, preferably 150 mmHg or lower.

The content of the solvent before and after drying can be measured by methods such as calorimetric analysis and differential thermal analysis.

The present invention is characterized in that a solvent (especially water) containing an iron component of 0.05 ppm or less is used in the method for producing compound (I). It is preferable to use a solvent such as water containing a very small amount of iron components throughout the production steps. However, it is not always used in all process steps. As mentioned above, the iron component is capable of forming complexes with compound (I), especially when the pH is between 5-7. Therefore, it is advantageous to use water containing very small amounts of iron components, especially in process steps where pH control is difficult. Therefore, in the reaction step of producing compound (I) and/or in the purification step of removing compounds other than compound (I) from the reaction mixture containing compound (I), the solvent containing a very small amount of iron components such as water Use is preferred. In the present invention, "the content of iron components" refers to the content of iron, iron compounds and iron ions (including ions containing iron atoms) in water used and the like. These iron components, in the form existing in water and the like or reacting with acids or bases to become iron ions or ions containing iron atoms, can form colored complexes with compound (I).

Examples of methods for obtaining a solvent containing an iron component of 0.05 ppm or less are known methods in the prior art, such as in the case of water as the solvent, distillation of industrial water (distilled water), and flow of industrial water through filling Purification of the column that has the function of capturing iron components such as ion exchange resin (water flowing through the water purifier, ion exchange water, etc.). The content of iron components in water can be measured with measuring equipment such as UV or visible light spectrophotometer, inductively coupled high frequency plasma-atomic emission spectrometer, atomic absorption analyzer, photoelectric photometer and colorimeter.

The present invention is characterized by a method for producing compound (I) using a reaction or purification vessel (hereinafter referred to as "vessel") having a corrosion-resistant layer on the inner wall. It is preferred to use containers with corrosion-resistant layers throughout the production steps. However, it is not always necessary to use them in all process steps. Multiple containers can be effectively used when there is a risk of iron components and the like causing coloring of the compound (I) leaching out of the container into solution due to corrosion. It is therefore preferable to use a reaction vessel having a corrosion-resistant layer in the reaction step for producing compound (I) and/or in the purification step for removing compounds other than compound (I) from a reaction mixture containing compound (I).

There are no particular limitations on the materials used for the corrosion-resistant layer if they are not corroded by acids such as sulfuric acid, or alkalis such as sodium hydroxide used in the reaction or purification steps.

Examples of corrosion-resistant materials include corrosion-resistant metals such as titanium, zirconium, tantalum, niobium, and nickel; glasses such as borosilicate glass, neutral glass, quartz glass, and alkali-resistant glass; inorganic materials such as enamel; organic materials including fluororesins Such as tetrafluoroethylene resin (PTFE or TFE), tetrafluoroethylene-perfluoroalkoxy vinyl ether copolymer (PFA), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), polychlorotrifluoroethylene (PCTFE) ), tetrafluoroethylene-ethylene copolymer (ETFE), chlorotrifluoroethylene-ethylene copolymer (ECTFE), polyvinylidene fluoride (PVDF) and polyvinyl fluoride (PVF).

An example of a method of forming a corrosion-resistant layer on the inner wall is lining or coating of a corrosion-resistant material on the inner wall. As for the method of lining or coating, when glass is used, an example is glass lining, that is, glass glaze is baked on the surface of the base material (steel plate) constituting the container. When a fluororesin is used, coating of baked powder and sheet back coating using glass cloth are exemplified. Among them, a container whose inner wall is lined or coated with glass or fluororesin is preferably used in view of heat resistance, durability and other factors. It is more advantageous to use vessels whose inner walls are lined with glass (commonly known as GL).

In the present invention, any one of the following methods is suitable: (a) using water having an iron component content of 0.05 ppm or less as a reaction solvent and/or a purification solvent, performing the reaction in the same SUS vessel as before ; (b) use the same industrial water as before, and carry out the reaction in a container with a corrosion-resistant layer on the inner wall; or (c) use water containing 0.05 ppm or less of iron components as a reaction solvent and/or purify solvents and also use containers with a corrosion-resistant layer on the inner wall. The method (c) is particularly preferable from the viewpoint of safer production of an uncolored, high-purity diphenylsulfone compound.

The reaction mixture may be colored in the purification step of removing compounds other than compound (I) from the reaction mixture containing compound (I). This is considered to be attributable to the dissolution of metals including iron ions, nickel ions and chromium ions from the SUS reaction vessel which is often used as a reaction vessel in the process step of reacting compound (II) such as BPS with compound (III) ions, or these metal ions contained in very small amounts in the water used in the process step of purifying the reaction mixture (industrial water) combine with phenolic compounds such as compound (I) to form complexes, which color the reaction solution . Once colored, it is difficult to decolorize the solution, even after repeated purifications. Therefore, in the present invention, a chelating agent is added to the reaction mixture in the process step of purifying the reaction mixture, and traps metal ions by chelation to prevent coloring.

The chelating agents used are not particularly limited as long as they are compounds that bind metal ions to form chelates. Examples include compounds obtained from the reaction of compounds having amino groups such as ammonia, polyamines, and amino acids with carbon disulfide, halogenated carboxylic acids, halogenated alcohols, etc.; and salts of these compounds; and dithiocarbamates; diacetyl oximes; dithizone, bipyridyl and phenanthroline.

Examples of polyamines include ethylenediamine, N-methylethylenediamine, N,N'-dimethylethylenediamine, 1,2-diaminopropane, 1,3-diaminopropane, diethylenetri Amines, triethylenetetramine, tetramethylenepentamine, and pentamethylenehexamine.

Examples of the halogenated carboxylic acid include monochloroacetic acid, monobromoacetic acid, monoiodoacetic acid, 1-chloropropionic acid, 2-chloropropionic acid, 1-bromopropionic acid and 2-bromopropionic acid.

Examples of halohydrins include 1-chloroethanol, 2-chloroethanol, 1-bromoethanol, 2-bromoethanol, 1-chloropropanol, 2-chloropropanol, 2-chloroisopropanol, 3-chloropropanol , 1-bromopropanol, 2-bromopropanol, 2-bromoisopropanol and 3-bromopropanol.

Examples of chelating agents include dithiocarbamates, such as sodium dithiocarbamate and potassium dithiocarbamate; acetic acid derivatives of amines, such as ethylenediaminetetraacetic acid (EDTA), hydroxyethyliminodi Acetic acid (HIDA), nitrilotriacetic acid (NTA), hydroxyethylethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTHA) and triethylenetetraminehexaacetic acid (TTHA); and Salts of these acetic acid derivatives (for example, alkali metal salts such as sodium and potassium salts; alkaline earth metal salts such as calcium and magnesium salts; and ammonium salts); ethanolamines such as ethanolamine, N,N'-bis(2-hydroxyethyl) Ethylenediamine, N,N',N'''-tris(2-hydroxyethyl)ethylenediamine and dihydroxyethylglycine (DHEG); salts of dithiocarbamic acid derivatives of polyamines, such as N , N'-bis(dithiocarboxy)ethylenediamine sodium salt, N,N'-bis(dithiocarboxy)ethylenediamine potassium salt, N,N'-bis(dithiocarboxy)trimethylene Diamine sodium salt, N,N'-bis(dithiocarboxy)trimethylenediamine potassium salt, N,N-bis(dithiocarboxy)diethylenetriamine sodium salt, N,N'- Bis(dithiocarboxy)diethylenetriamine potassium salt, N,N',N"-tris(dithiocarboxy)diethylenetriamine sodium salt, N,N',N"-tri( Dithiocarboxy)diethylenetriamine potassium salt, N,N'-bis(dithiocarboxy)triethylenetetramine sodium salt, N,N'-bis(dithiocarboxy)triethylenetetramine Amine potassium salt, N,N′,N″-tris(dithiocarboxy)triethylenetetramine sodium salt and N,N′N″-tris(dithiocarboxy)triethylenetetramine potassium salt; Diketoxime, dithizone, bipyridyl and phenanthroline.

Among these chelating agents, preferred is a chelating agent (water-soluble chelating agent) that can form a water-soluble chelate represented by the chelating agent obtained by reacting ammonia or polyamine with a halogenated carboxylic acid and/or a halogenated alcohol; and these Reagent salts. The use of EDTA or a salt thereof is particularly preferred because of ease of acquisition, handling, ease of isolation, and the like.

Examples of EDTA salts include EDTA disodium salt, EDTA trisodium salt, EDTA tetrasodium salt, EDTA dipotassium salt, EDTA tripotassium salt, EDTA tetrapotassium salt, EDTA calcium salt, EDTA tricalcium salt, EDTA diammonium salt and EDTA Dipotassium magnesium salt. When a water-soluble chelating agent is added to the reaction mixture, the resulting chelate is water-soluble and will not be entrapped in the crystals of 4,4'-dihydroxydiphenylsulfone. Thus, a completely decolorized target compound was produced.

The chelating agent can be added in any of the following stages: (a) after the end of the reaction and before the removal of the unreacted compound (III), (b) after the removal of the compound (III) and at the 4,4'- Before removal of dihydroxydiphenylsulfone diether, (c) after removal of 4,4'-dihydroxydiphenylsulfone diether and before removal of unreacted compound (II) with pH adjustment, and (d) after After removing unreacted compound (II) with pH adjustment. Among them, (d) is preferable, that is, adding the chelating agent after the pH is adjusted to remove the unreacted compound (II). Adding a water-soluble chelating agent at the same time as water is added to the reaction mixture is particularly preferred because metal ions in water are chelated to form water-soluble chelates which are easily separated. The chelating agent can be added in several passes if desired. Chelating agents are commonly used in aqueous solutions. The amount of the reagent added is suitably determined according to the content of metal ions such as iron ions, nickel ions and chromium ions in the reaction mixture. If the added amount of the chelating agent is too small, the coloring preventing effect by adding the chelating agent is not satisfactory. On the other hand, if the agent is added too much, the coloring preventing effect is satisfactory but the excess chelating agent may be mixed as an impurity into the final product of compound (I). Therefore, it is advantageous to measure the concentration of metal ions contained in the reaction mixture by known methods before adding the reagent, and then to add an amount of chelating agent corresponding to the concentration of metal ions. The amount of the chelating agent added is usually 0.0001-0.5 parts by weight, preferably 0.001-0.1 parts by weight, relative to 100 parts by weight of the reaction mixture.

Inventions related to the above (Element 7), (Element 15), (Element 18), (Element 24), (Element 26), (Element 27), (Element 28) and (Element 31) are suitable for use in the production of compounds ( In the method of I), the compound has a b value of 2.5 or less when measured by a colorimeter or is visually white. Compound (I) is preferably a whiter product when used as a developer. The production method of the prior art has a problem that it is impossible to provide the product stably. This problem is solved by using the method of the present invention. The best way to implement the invention:

The present invention is described in detail with reference to the examples. The present invention is not limited to the following examples. Compound (II), solvent type, container type used in the reaction and purification steps and other conditions can be changed freely as long as they do not deviate from the gist of the present invention.

Distilled water was used in Reference Example 1, Examples 1-3 and Comparative Examples 1-4. The content of metal ions in distilled water was 0.05 ppm or less as measured by inductively coupled plasma-atomic emission spectroscopy.

In Reference Example 1, Examples 1-3, and Comparative Examples 1-4, a vessel whose inner wall was lined with glass (hereinafter referred to as a GL vessel) was used as a reaction and purification vessel.

Reference Example 1

Add 450 g of 4,4'-dihydroxydiphenylsulfone (BPS), 255 mL of 48% aqueous sodium hydroxide solution and 120 mL of water into the reaction vessel, mix under stirring to make the entire solution uniform, while the temperature rises to 75°C. 225 g of isopropyl bromide was slowly added dropwise to the resulting solution at 55±3°C. After the end of the dropwise addition, the resulting solution was continued to be stirred at 55±5° C. for a total of 20 hours from the start of the dropwise addition. The resulting reaction solution was used for purification in Example 1 and Comparative Example 1. Example 1: Purification of a mixture containing 4-isopropoxy-4'-hydroxydiphenylsulfone and impurities [(element (1) to (element 6))

235 mL of warm water was added to the reaction solution and heated at 80° C. for one hour to evaporate unreacted isopropyl bromide to remove it. Then, 300 mL of warm water and 250 mL of toluene were added at 80° C. with sufficient stirring. The aqueous layer was separated.

(1) The first pH adjustment

To the obtained aqueous layer, 1100 mL of toluene and 200 mL of water were added at 79° C., and stirred at the same temperature for 30 minutes. Further, 30% dilute sulfuric acid was added dropwise at 82° C. under stirring for 1 hour to uniformly adjust the pH of the aqueous layer of the reaction solution to 8.4-8.7. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

(2) The second pH adjustment

Add 300 mL of toluene and 300 mL of water to the obtained toluene layer at 82°C, add 30% dilute sulfuric acid dropwise at 82°C for 1 hour with stirring, and adjust the pH of the aqueous layer to 8.3-8.6 uniformly. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

To the toluene layer were added 250 mL of toluene and 250 mL of water at 82° C., followed by stirring at the same temperature for 2 hours. Then, the resulting solution was left at 82°C for 30 minutes and the toluene layer was separated. The resulting toluene layer was cooled to deposit crystals. The crystals were separated by filtration, washed with toluene and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%).

Analysis of product purity by high performance liquid chromatography showed the presence of 99.83 wt% 4-isopropoxy-4'-hydroxydiphenylsulfone and 0.01 wt% BPS.

Comparative Example 1: Purification of a mixture containing 4-isopropoxy-4'-hydroxyl diphenyl sulfone and impurities [comparative example with Example 1]

235 mL of warm water was added to the reaction solution obtained in Reference Example 1 and unreacted isopropyl bromide was evaporated by heating at 80° C. to remove it. Then, 300 mL of warm water and 250 mL of toluene were added at 80° C. with sufficient stirring. The aqueous layer was separated.

To the obtained aqueous layer, 1100 mL of toluene and 200 mL of water were added at 79° C., and stirred at the same temperature for 30 minutes. Furthermore, 30% dilute sulfuric acid was added dropwise at 82° C. under stirring for 1 hour to uniformly adjust the pH of the aqueous layer to 8.4-8.7. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

To the toluene layer were added 250 mL of toluene and 250 mL of water at 82° C., followed by stirring at the same temperature for 2 hours. Then, the resulting solution was left at 82°C for 30 minutes and the toluene layer was separated.

The resulting toluene layer was cooled to deposit crystals. The crystals were separated by filtration, washed with toluene and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%).

Analysis of product purity by high performance liquid chromatography showed the presence of 98.4 wt% 4-isopropoxy-4'-hydroxydiphenylsulfone and 1.5 wt% BPS.

Embodiment 2 [Embodiments of (Element 15) to (Element 17)]

Add 450 g of 4,4'-dihydroxydiphenylsulfone (BPS), 255 mL of 48% aqueous sodium hydroxide solution and 120 mL of water into the reaction vessel, mix under stirring to make the entire solution uniform, while the temperature rises to 75°C. 225 g of isopropyl bromide was slowly added dropwise to the resulting solution at 55±3°C. After the end of the dropwise addition, the resulting solution was continued to be stirred at 55±5° C. for a total of 20 hours from the start of the dropwise addition.

235 mL of warm water was added to the reaction solution and heated at 80° C. for one hour to evaporate unreacted isopropyl bromide to remove it. Then, 300 mL of warm water and 250 mL of toluene were added at 80° C. with sufficient stirring. The aqueous layer was separated.

To the obtained aqueous layer, 1100 mL of toluene and 200 mL of water were added at 79° C., and stirred at the same temperature for 30 minutes. The toluene used at this time was toluene recovered from the solvent used for the crystallization of 4-isopropoxy-4'-hydroxydiphenylsulfone. The content of isopropyl bromide in the toluene layer was 0.5 wt%. Further, 30% dilute sulfuric acid was added dropwise at 82° C. under stirring for 1 hour to uniformly adjust the pH of the aqueous layer of the reaction solution to 8.4-8.7. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

300 mL of toluene and 300 mL of water were added to the obtained toluene layer at 82° C., and 30% dilute sulfuric acid was added dropwise at 82° C. with stirring for 1 hour to uniformly adjust the pH of the aqueous layer to 8.3 to 8.6. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

To the toluene layer were added 250 mL of toluene and 250 mL of water at 82° C., followed by stirring at the same temperature for 2 hours. Then, the resulting solution was left at 82°C for 30 minutes and the toluene layer was separated. The resulting toluene layer was cooled to deposit crystals. The crystals were separated by filtration, washed with toluene and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%).

Analysis of product purity by high performance liquid chromatography showed the presence of 99.83 wt% 4-isopropoxy-4'-hydroxydiphenylsulfone and 0.01 wt% BPS. The product was measured by a colorimeter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) to show a b value of 2.5 or less. No coloring was observed.

Comparative Example 2 [Example Contrasted with Example 2]

Repeat Example 2, just add reclaimed toluene to adjust the pH and the content of isopropyl bromide in the toluene layer is 5.5 wt%, to obtain 4-isopropoxy-4'-hydroxyl diphenyl with the same yield and purity base sulfone. However, the product was visually yellow.

Embodiment 3 [Embodiments of (Element 7) to (Element 14)]

210g of BPS, 74.2mL of 48% aqueous sodium hydroxide solution and 740mL of water were added to the reaction vessel and mixed under stirring to make the whole solution uniform while the temperature was raised to 80°C. 705 mL of toluene was added to the resulting solution at 70°C and 165 g of isopropyl bromide (iPr-Br) was added dropwise with stirring. The resulting solution was stirred at 76-80°C for 8 hours. Then, 4.8 mL of 48% aqueous sodium hydroxide solution and 22 g of isopropyl bromide were added, and stirred at 78-80° C. for 6 hours. In addition, 3.3 mL of 48% aqueous sodium hydroxide solution and 25 g of isopropyl bromide were added and reacted at 78-81°C for 8 hours.

After the reaction was completed, 300 mL of toluene was added to the reaction solution and heated at 80° C. for 3 hours to evaporate unreacted isopropyl bromide to completely remove it.

Then, 200 mL of water, 694 mL of toluene, 2.5 g of anhydrous sodium carbonate (soda ash) and 10 mL of warm water were added to the reaction solution, and 48% aqueous sodium hydroxide was added to adjust the pH of the reaction solution to 8.55±0.02. The resulting solution was left standing for 30 minutes and the toluene layer was separated. To the toluene layer was added 500 mL of water and 800 mL of toluene at 75-80 °C. The resulting solution was stirred at the same temperature for 30 minutes and left to stand for 30 minutes. The toluene layer was separated and cooled. The deposited crystals were separated by filtration, washed with water and dried to obtain 171.7 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%). At this time, the content of isopropyl bromide in the toluene layer was 0.5 wt% as measured by gas chromatography.

The obtained 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 99% or more, and a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) of 2.5 or a b-value below 2.5. No coloring was observed.

Embodiment 4 [Embodiments of (Element 18) to (Element 23)]

450 g of BPS, 255 mL of 48% aqueous sodium hydroxide solution and 120 mL of water were added to the reaction vessel and mixed under stirring to make the entire solution uniform while the temperature was raised to 75 °C. 225 g of isopropyl bromide was slowly added dropwise to the resulting solution at 55±3°C. Stirring of the resulting solution was further continued at 55±5° C. after the dropwise addition was completed.

The reaction was stopped when a total of 20 hours had elapsed from the start of the dropwise addition. A portion of the reaction solution was taken as a sample and analyzed by high performance liquid chromatography (HPLC). The results showed 67% 4-isopropoxy-4'-hydroxydiphenylsulfone, 32% BPS and 1% 4,4'-diisopropoxydiphenylsulfone. The reaction solution was heated at 80°C for 1 hour to remove unreacted isopropyl bromide by evaporating it. In addition, 24 mL of warm water (0.05 parts by weight, relative to 1 part by weight of BPS) was added to the reaction solution and heated at 80°C for 1 hour, and then another 235 mL of warm water was added and heated at 80°C for 1 hour to evaporate unreacted iso Propyl bromide to remove it. A portion of the reaction solution was taken as a sample and analyzed by HPLC. The results showed 70% 4-isopropoxy-4'-hydroxydiphenylsulfone, 29% BPS and 1% 4,4'-diisopropoxydiphenylsulfone. No increase in by-product 4,4'-diisopropoxydiphenylsulfone was observed. Then, 300 mL of warm water and 250 mL of toluene were added for thorough stirring, and then the aqueous layer was separated.

1100 mL of toluene and 200 mL of water were added to the aqueous layer at 79° C., and stirred at the same temperature for 30 minutes. Furthermore, 30% dilute sulfuric acid was added dropwise at 82° C. under stirring for 1 hour to uniformly adjust the pH of the reaction solution to 8.4-8.7. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

Add 300mL toluene and 300mL water to the toluene layer at 82°C, add 30% dilute sulfuric acid dropwise at 82°C for 1 hour with stirring, and adjust the pH of the entire solution to 8.3-8.6 evenly. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated. Further, 250 mL of toluene and 250 mL of water were added to the toluene layer at 82° C., and stirred at the same temperature for 2 hours. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

The toluene layer was cooled to 10-35°C to deposit crystals. The crystals were separated by filtration, washed with water and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%). At this time, the content of isopropyl bromide in the toluene layer was 0.8 wt% as measured by gas chromatography.

The obtained powder of 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 99% or more, and had a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001DP) A b-value of 2.5 or less. No coloring was observed.

Comparative Example 3 [Example Contrasted with Example 3]

Example 2 was repeated to obtain 171.7 g of 4-isopropoxy-4'-hydroxyl diphenyl sulfone (yield: 70%) in the form of powder, except that after the reaction was finished, by adding 300 mL of toluene to the reaction solution, at 80 ° C for 3 hours to remove unreacted isopropyl bromide process steps.

The product had a purity of 99% or more, and a b value of 4.1 measured by a colorimeter (manufactured by NipponDenshoku Kogyo Co., Ltd, model: 1001 DP). It appears bright yellow.

Comparative Example 4 [Example Contrasted with Example 4]

450 g of BPS, 255 mL of 48% aqueous sodium hydroxide solution and 120 mL of water were added to the reaction vessel and mixed under stirring to make the entire solution uniform while the temperature was raised to 75 °C. 225 g of isopropyl bromide was slowly added dropwise to the resulting solution at 55±3°C. Stirring of the resulting solution was further continued at 55±5° C. after the dropwise addition was completed.

The reaction was stopped when a total of 20 hours had elapsed from the start of the dropwise addition. A portion of the reaction solution was taken as a sample and analyzed by high performance liquid chromatography (HPLC). The results showed 67% of 4-isopropoxy-4'-hydroxydiphenylsulfone, 32% of BPS and 1% of 4,4'-diisopropoxydiphenylsulfone. 235 mL of warm water (0.52 parts by weight relative to 1 part by weight of BPS) was added to the reaction solution and heated at 80° C. for 1 hour to evaporate unreacted isopropyl bromide to remove it. A portion of the reaction solution was taken as a sample and analyzed by HPLC. The results showed 70% of 4-isopropoxy-4'-hydroxydiphenylsulfone, 26% of BPS and 4% of 4,4'-diisopropoxydiphenylsulfone. An increase in by-product 4,4'-diisopropoxydiphenylsulfone was observed. Then, at 80° C., 300 mL of warm water and 250 mL of toluene were added and sufficiently stirred, and then the water layer was separated.

1100 mL of toluene and 200 mL of water were added to the aqueous layer at 79° C., and stirred at the same temperature for 30 minutes. Furthermore, 30% dilute sulfuric acid was added dropwise at 82° C. under stirring for 1 hour to uniformly adjust the pH of the reaction solution to 8.4-8.7. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

Add 300mL toluene and 300mL water to the toluene layer at 82°C, add 30% dilute sulfuric acid dropwise at 82°C for 1 hour with stirring, and adjust the pH of the entire solution to 8.3-8.6 evenly. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated. Further, 250 mL of toluene and 250 mL of water were added to the toluene layer at 82° C., and stirred at the same temperature for 2 hours. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

The toluene layer was cooled to 10-35°C to deposit crystals. The crystals were separated by filtration, washed with water and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%). At this time, the amount of isopropyl bromide contained in the toluene layer was 0.8 wt% as measured by gas chromatography.

The obtained powder of 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 99% or more, and had a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001DP) A b-value of 2.5 or less. No coloring was observed.

Embodiment 5 [Embodiments of (Element 24) to (Element 30)]

In Example 5 and Reference Example 2, distilled water was used in all cases. In Comparative Example 5 and Reference Example 3, all industrial water was used. The iron content of distilled and industrial water was measured by inductively coupled plasma-atomic emission spectroscopy. The former contained 0.05 ppm or less of the iron component and the latter contained 0.26 ppm.

A GL vessel was used as a reaction and purification vessel in Example 5 and Reference Example 2, and an SUS vessel commonly used in the prior art was used in Comparative Example 5 and Reference Example 3.

Add 450g of 4,4'-dihydroxydiphenylsulfone (BPS), 255mL of 48% aqueous sodium hydroxide solution and 120mL of distilled water into the GL container, mix under stirring to make the whole solution uniform, while the temperature is raised to 75°C. 225 g of isopropyl bromide was slowly added dropwise to the resulting solution at 55±3°C. Stirring of the resulting solution was further continued at 55±5° C. after the dropwise addition was completed. When 20 hours had elapsed from the start of the dropwise addition, 235 mL of distilled water was added to the reaction solution at 80°C. The resulting solution was heated at 80°C for 1 hour to remove unreacted isopropyl bromide by evaporation. Then, 300 mL of distilled water and 250 mL of toluene were added at 80° C. for sufficient stirring, and then the water layer was separated.

Then, 1100 mL of toluene and 200 mL of distilled water were added to the aqueous layer at 79° C., and stirred at the same temperature for 30 minutes. Furthermore, 30% dilute sulfuric acid was added dropwise at 82° C. under stirring for 1 hour to uniformly adjust the pH of the reaction solution to 8.3-8.7. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated. Further, 250 mL of toluene and 250 mL of water were added to the toluene layer at 82° C., and stirred at the same temperature for 2 hours. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

The resulting toluene layer was cooled to deposit crystals. The crystals were separated by filtration, washed with water and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%).

The obtained 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 98% or more, and a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) of 2.5 or a b-value below 2.5. No coloring was observed.

Comparative Example 5 [Example Contrasted with Example 5]

Example 4 was repeated to obtain 368.0 g of 4-isopropoxy-4'-hydroxydiphenylsulfone in powder form (yield: 70%), except that a SUS container was used instead of a GL container and industrial water was used instead of distilled water.

The obtained 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 98% or more, and a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) of 4.1 the b-value. It comes in bright pink color.

Reference Example 2

Wherein x is an integer of 1-10.

Add 47.5mL of distilled water, 25.6g of sodium hydroxide and 80.0g of 4,4'-dihydroxydiphenyl sulfone into the GL container, stir and dissolve at 110±2°C for 4 hours. To the resulting solution was added 20.34 g of bis(2-chloroethyl)ether at 110-112°C and stirred at the same temperature for 8 hours. After the reaction was finished, 108.1 mL of hot water was added to the reaction solution and cooled to 80°C. At 70° C., 167.4 mL of 90% aqueous methanol solution was added and stirred for 30 minutes to make the solution uniform. Then, 116.4 g of 10% hydrochloric acid was slowly added dropwise at 71°C to bring the pH to 4-5. The resulting solution was held at 71°C for one hour, cooled to 25-30°C, and held for a further 8 hours. The deposited crystals were separated by filtration, washed with 200 mL of 50% methanol aqueous solution and dried to obtain 63.2 g of the target compound in powder form. Yield: 78%.

The obtained target compound had a purity of 99% or more, and a b value of 2.5 or less as measured by a colorimeter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP). No coloring was observed.

Reference Example 3

Reference Example 2 was repeated to obtain 63.2 g of the target compound in powder form (yield: 78%) except that a SUS container was used instead of a GL container and industrial water was used instead of distilled water.

The obtained target compound had a purity of 98% or more, and a b value of 4.1 measured by a colorimeter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP). It comes in bright pink color.

Embodiment 6 [the embodiment of (element 31)]

The water used in Examples 6 and 7, Comparative Example 6 and Reference Examples 4 and 5 was industrial water. Measurements by inductively coupled plasma-atomic emission spectroscopy have shown that the content of metal ions in industrial water is 0.1 ppm or more.

450g of 4,4'-dihydroxydiphenylsulfone (BPS), 255mL of 48% aqueous sodium hydroxide solution and 120mL of water were added to the SUS reaction vessel, mixed under stirring to make the whole solution uniform while the temperature was raised to 75°C. 225 g of isopropyl bromide was slowly added dropwise to the resulting solution at 55±3°C. Stirring of the resulting solution was further continued at 55±5° C. after the dropwise addition was completed. When a total of 20 hours had elapsed since the dropwise addition started, 235 mL of warm water was added to the reaction solution. The resulting solution was heated at 80°C for 1 hour to remove unreacted isopropyl bromide by evaporating it. Then, 300 mL of warm water and 250 mL of toluene were added at 80° C. for thorough stirring, and then the aqueous layer was separated.

Then, 1100 mL of toluene and 200 mL of water were added to the aqueous layer at 79° C., and stirred at the same temperature for 30 minutes. Further, 30% dilute sulfuric acid was added dropwise at 82° C. with stirring over 1 hour to uniformly adjust the pH of the reaction solution to 8.3-8.7, and then 2.7 mL of 5% EDTA disodium salt solution was added. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated. Further, 250 mL of toluene and 250 mL of water were added to the toluene layer at 82° C., and stirred at the same temperature for 2 hours. The resulting solution was left standing at 82°C for 30 minutes and the toluene layer was separated.

Cool the toluene layer to deposit crystals. The crystals were separated by filtration, washed with water and dried to obtain 368.0 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%).

The obtained 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 98% or more, and a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) of 2.5 or a b-value below 2.5. No coloring was observed.

Embodiment 7 [the embodiment of (element 31)]

Add 210g of 4,4'-dihydroxydiphenyl sulfone (BPS), 74.2mL of 48% aqueous sodium hydroxide solution and 740mL of water into the SUS reaction vessel, mix under stirring to make the whole solution uniform, while raising the temperature to 80°C . To the resulting solution was added 705 mL of toluene at 70°C, and 165 g of isopropyl bromide (iPr-Br) was slowly added dropwise. The resulting solution was stirred at 76-80°C for 8 hours. Then, 4.8 mL of 48% aqueous sodium hydroxide solution and 22 g of isopropyl bromide were added, and stirred at 78-80° C. for 6 hours. Furthermore, 3.3 mL of 48% aqueous sodium hydroxide solution and 25 g of isopropyl bromide were added, and the mixture was reacted at 78-81° C. for 8 hours. After the reaction ended, 300 mL of toluene was added to the reaction solution, and heated at 80° C. for 3 hours to evaporate unreacted isopropyl bromide to completely remove it.

Then, 200 mL of water, 694 mL of toluene, 2.5 g of anhydrous sodium carbonate (soda ash) and 10 mL of warm water were added, and 48% aqueous sodium hydroxide solution was added to adjust the pH of the reaction solution to 8.55±0.02. To the resulting solution was added 1.2 mL of 5% EDTA disodium saline solution and left to stand for 30 minutes. Then the toluene layer was separated. 500 mL of water and 800 mL of toluene were added to the toluene layer at 75-80° C., and stirred at the same temperature for 30 minutes. The toluene layer was separated.

Cool the toluene layer. The deposited crystals were separated by filtration, washed with water and dried to obtain 171.7 g of the target compound, 4-isopropoxy-4'-hydroxydiphenylsulfone, in the form of powder (yield: 70%).

The obtained 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 98% or more, and a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) of 2.5 or a b-value below 2.5. No coloring was observed.

Comparative Example 6 [Example Contrasted with Example 5]

Example 5 was repeated to obtain 368.0 g of 4-isopropoxy-4'-hydroxydiphenylsulfone in powder form (yield: 70%) except that 5% EDTA disodium salt aqueous solution was added to the reaction solution in the purification step operation is omitted.

The obtained 4-isopropoxy-4'-hydroxydiphenyl sulfone had a purity of 98% or more, and a color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP) of 4.1 the b-value. It appears bright yellow.

Reference Example 4: Production of the same target compound as in Reference Example 2

Add 47.5mL of water, 25.6g of sodium hydroxide and 80.0g of 4,4'-dihydroxydiphenyl sulfone into a 500mL four-necked flask and stir to dissolve at 110±2°C for 4 hours. 20.34 g of bis(2-chloroethyl)ether was added to the resulting solution at 110-112°C and stirred at the same temperature for 8 hours. After the reaction was finished, 108.1 mL of hot water was added to the reaction solution and cooled to 80°C. 167.4 mL of 90% methanol aqueous solution was added to the resulting solution and stirred for 30 minutes to make the solution uniform. Then, 0.5 mL of 5% EDTA disodium salt solution was added and 116.4 g of 10% hydrochloric acid was slowly added dropwise at 71° C. to adjust the pH to 4-5. The resulting solution was held at 71°C for one hour, cooled to 25-30°C, and held for a further 8 hours. The deposited crystals were separated by filtration, washed with 200 mL of 50% methanol aqueous solution, and dried to obtain 63.2 g of the target compound in powder form. Yield: 78%.

The target compound has a purity of 99% or more, and a b value of 2.5 or less as measured by a colorimeter (manufactured by NipponDenshoku Kogyo Co., Ltd, model: 1001 DP). No coloring was observed.

Reference Example 5

Reference Example 4 was repeated to obtain 63.2 g of the target compound in powder form (yield: 78%) except that the addition of 5% EDTA disodium salt solution to the reaction solution in the purification step was omitted.

The obtained target compound had a purity of 98% or more, and a b value of 4.1 measured by a colorimeter (manufactured by Nippon Denshoku Kogyo Co., Ltd, model: 1001 DP). It appears bright yellow.

Embodiment 7 [Embodiments of (Element 32) to (Element 37)]

577 g of 4-isopropoxy-4'-hydroxydiphenylsulfone (crystallized and filtered from toluene in the same manner as in Reference Example 1 and Example 1 and not yet dried) forms molecular compounds with toluene and has Attached toluene solvents other than solvated toluene. Before drying, 4-isopropoxy-4'-hydroxydiphenyl sulfone was heated and dried under reduced pressure with a paddle drier under the following operating conditions:

Decompression degree: 60-150mmHg

Heating temperature: 80-85°C

Stirring speed: 2-3 rpm

Drying time: 16 hours

4-Isopropoxy-4'-hydroxydiphenylsulfone contains 0.1 wt% or less toluene after the compound is dried. No lumpy particles were observed. The product is easily comminuted into fine particles even in the subsequent pulverization process step.

Comparative Example 7 [Example Contrasted with Example 7]

4-Isopropoxy-4'-hydroxydiphenyl sulfone having the same conditions as in Example 7 was dried by heating under the same conditions as those in Example 8, except that heating under reduced pressure was used without a stirring device. The dryer replaces the paddle dryer. A large number of lumpy particles were observed after the compound dried. The compound after drying was heavier than that in Example 7. In addition to this, it takes a long time in the subsequent comminution process step to comminute the compound to the particle size predetermined for the product.

Industrial Applicability:

As described above, the present invention relates to a method for producing 4,4'-dihydroxydiphenylsulfone monoether in which an uncolored, high-purity target compound can be efficiently removed from mixtures containing even high concentrations of the target compound and impurities separate from.

4,4'-Dihydroxydiphenylsulfone monoether is a compound useful as a developer. The method of the present invention stably provides a product of high quality and industrially high use value.

Claims (7)

1. the method for a preparation formula (I) compound:

R wherein ¹And R ²Be halogen independently of one another, have the alkyl of 1-8 carbon atom or have the alkenyl of 2-8 carbon atom; M and n are 0 or the integer of 1-4 independently of one another; And R ³Be the alkyl with 1-8 carbon atom, alkenyl, cycloalkyl or aralkyl with 3-8 carbon atom with 2-8 carbon atom, it is characterized in that in the method for production formula (I) compound with drying process step, in the drying process step under mechanical stirring desciccate.

2. according to the method for preparation formula (I) compound of claim 1, wherein under mechanical stirring under reduced pressure with the product heat drying.

3. according to the method for preparation formula (I) compound of claim 1 or 2, wherein be in the state of the performance that melts under the temperature with the fusing point that is being lower than formula (I) compound at formula before the drying (1) compound.

4. according to the method for each preparation formula (I) compound among the claim 1-3, wherein formula (I) compound is in the state that forms molecular compound with solvent before drying.

5. according to the method for preparation formula (I) compound of claim 4, wherein solvent is an organic solvent.

6. according to the method for preparation formula (I) compound of claim 5, wherein organic solvent is an aromatic hydrocarbons.

7. according to the method for each preparation formula (I) compound among the claim 1-6, its Chinese style (I) compound is a compound shown in the formula (IV):

R wherein ³Be the alkyl with 1-8 carbon atom, alkenyl, cycloalkyl or aralkyl with 3-8 carbon atom with 2-8 carbon atom.