A method for preparing a tetrabromophenol tetrahalosulfonophthalein

Abstract

The present application relates to the technical field of chemical medicine preparation, and particularly relates to a preparation method of tetrabromophenol tetrahalosulfonophthalein, which is prepared from 3,4,5,6-tetrahalophenol sulfonophthalein as raw material, organic carboxylic acid in aqueous solution, liquid bromine, oxidation by hydrogen peroxide to obtain tetrabromophenol tetrahalosulfonophthalein crude product, then salification with alkali salt in an aprotic solvent to obtain tetrabromophenol tetrahalosulfonophthalein salt; and then acid conversion with organic carboxylic acid in aqueous solution, recrystallization to obtain tetrabromophenol tetrahalosulfonophthalein pure product; the present application provides a preparation method of tetrabromophenol tetrahalosulfonophthalein, which is low in cost, high in yield and purity, simple in method, mild in condition, high in yield and purity, and beneficial to mass production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical medicine preparation, and particularly relates to a preparation method of tetrabromo phenol tetrahalogenated sulfonephthalein. BACKGROUND

[0002] Tetrabromo phenol tetrahalogenated sulfonephthalein (TBPTHSP) belongs to sulfonephthalein compounds, is an important dye due to high stability and good color fixing effect, and has the following structure:

[0003]

[0004] In the formula (1), X can be Cl, Br or I; when X is Br, tetrabromo phenol tetrabromo sulfonephthalein is tetrabromo phenol blue, which is an important protein error indicator in clinical diagnosis and has been widely used in hair dyes in recent years.

[0005] The previous synthesis method of tetrabromo phenol tetrahalogenated sulfonephthalein is to use tetrabromo phenol sulfonephthalein as raw material, and tetrabromo phenol tetrahalogenated sulfonephthalein is prepared by bromination in glacial acetic acid. The method uses a large amount of liquid bromine, and a large amount of hydrogen bromide is generated in the reaction process and needs to be neutralized and disposed, which wastes reagents, and the reaction is not complete enough, the impurities are high, the purification is difficult, the yield is low, the purity is low, and it is difficult to mass-produce.

[0006] Therefore, how to develop a preparation method of tetrabromo phenol tetrahalogenated sulfonephthalein with high yield, high purity, low cost and beneficial to industrial production is a technical problem to be solved at present. SUMMARY

[0007] The present application aims to overcome the deficiencies of the prior art, and provide a preparation method of tetrabromo phenol tetrahalogenated sulfonephthalein with simple operation, high yield, high purity, low cost and beneficial to industrial production.

[0008] To achieve the above-mentioned purpose, the present application provides the following technical scheme:

[0009] A preparation method of tetrabromo phenol tetrahalogenated sulfonephthalein, which is prepared by using 3,4,5,6-tetrabromo phenol sulfonephthalein as raw material, and then carrying out bromination by hydrogen peroxide oxidation and liquid bromine in an aqueous solution of organic carboxylic acid to obtain tetrabromo phenol tetrahalogenated sulfonephthalein crude product; then salt formation with an alkali metal salt in a solvent to obtain tetrabromo phenol tetrahalogenated sulfonephthalein alkali metal salt; and then acid conversion with organic carboxylic acid in an aqueous solution, and recrystallization to obtain tetrabromo phenol tetrahalogenated sulfonephthalein pure product; the reaction formula is as follows:

[0010]

[0011] In formula (2), X is Cl, Br or I; M is Li, Na or K;

[0012] The 3,4,5,6-tetrahalophenol sulfonophthalein is 3,4,5,6-tetrachlorophenol sulfonophthalein, 3,4,5,6-tetrabromophenol sulfonophthalein or 3,4,5,6-tetraiodophenol sulfonophthalein;

[0013] The organic carboxylic acid is one of formic acid, acetic acid or propionic acid;

[0014] The alkali metal salt is one of carbonate, bicarbonate or acetate;

[0015] The solvent is an aprotic solvent;

[0016] The tetrahalophenol sulfonophthalein is 3,4,5,6-tetrachlorophenol sulfonophthalein, 3,4,5,6-tetrabromophenol sulfonophthalein or 3,4,5,6-tetraiodophenol sulfonophthalein.

[0017] The tetrahalophenol sulfonophthalein is 3,4,5,6-tetrachlorophenol sulfonophthalein, 3,4,5,6-tetrabromophenol sulfonophthalein or 3,4,5,6-tetraiodophenol sulfonophthalein.

[0018] The tetrahalophenol sulfonophthalein is 3,4,5,6-tetrachlorophenol sulfonophthalein, 3,4,5,6-tetrabromophenol sulfonophthalein or 3,4,5,6-tetraiodophenol sulfonophthalein.

[0019] A preparation method of a tetrahalophenol sulfonophthalein, the preparation method comprising the following specific steps:

[0020] 1) Oxidation bromination: a certain mass-volume ratio of an organic carboxylic acid is added to 3,4,5,6-tetrahalophenol sulfonophthalein (compound a), and then heated and stirred until uniform; a certain mass-volume ratio of water is added, and then cooled to room temperature; a certain molar ratio of hydrogen peroxide is added, and then stirred until uniform; a certain molar ratio of liquid bromine is added, and then stirred while controlling the temperature; after the reaction is completed, the reaction solution is cooled to room temperature, filtered, and then the filtrate is recovered and reused; the filter cake is collected and dried to obtain a tetrahalophenol sulfonophthalein crude product (compound b);

[0021] 2) Salt formation and purification: a certain mass-volume ratio of an aprotic solvent is added to the tetrahalophenol sulfonophthalein crude product, and then a certain molar ratio of an alkali metal salt is added; the mixture is stirred and reacted while controlling the temperature; after the reaction is completed, crystals are precipitated in the reaction solution, and then cooled to room temperature; the mixture is filtered, and then the filter cake is collected and dried to obtain a tetrahalophenol sulfonophthalein salt (compound c);

[0022] 3) The acid conversion purification: a certain mass-volume ratio of water is added to the tetrabromophenol tetrahalosulfonophthalein, a certain molar ratio of organic carboxylic acid is added, stirring, temperature control reaction; after the reaction is completed, recrystallization is carried out in the reaction solution, cooled to room temperature, filtered, collected the filter cake, dried, to obtain tetrabromophenol tetrahalosulfonophthalein pure product (compound b);

[0023] The 3,4,5,6-tetrahalophenol sulfonophthalein is 3,4,5,6-tetrachlorophenol sulfonophthalein, 3,4,5,6-tetrabromophenol sulfonophthalein or 3,4,5,6-tetraiodophenol sulfonophthalein;

[0024] The organic carboxylic acid is one of formic acid, acetic acid or propionic acid;

[0025] The alkali metal salt is one of carbonate, bicarbonate or acetate;

[0026] The aprotic solvent can be any one or a combination of two of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether;

[0027] The tetrabromophenol tetrahalosulfonophthalein salt is tetrabromophenol tetrachlorosulfonophthalein alkali metal salt, tetrabromophenol tetrabromosulfonophthalein alkali metal salt or tetrabromophenol tetraiodosulfonophthalein alkali metal salt;

[0028] The tetrabromophenol tetrachlorosulfonophthalein salt is tetrabromophenol tetrachlorosulfonophthalein lithium salt, tetrabromophenol tetrachlorosulfonophthalein sodium salt or tetrabromophenol tetrachlorosulfonophthalein potassium salt; the tetrabromophenol tetrabromosulfonophthalein salt is tetrabromophenol tetrabromosulfonophthalein lithium salt, tetrabromophenol tetrabromosulfonophthalein sodium salt, tetrabromophenol tetrabromosulfonophthalein potassium salt; the tetrabromophenol tetraiodosulfonophthalein salt is tetrabromophenol tetraiodosulfonophthalein lithium salt, tetrabromophenol tetraiodosulfonophthalein sodium salt, tetrabromophenol tetraiodosulfonophthalein potassium salt;

[0029] The tetrabromophenol tetrahalosulfonophthalein is tetrabromophenol tetrachlorosulfonophthalein, tetrabromophenol tetrabromosulfonophthalein or tetrabromophenol tetraiodosulfonophthalein.

[0030] The experimental results of the oxidation and bromination steps of the present application show that:

[0031] When the acid selected by the present application is an organic carboxylic acid, the solubility of the phenol sulfonophthalein is better, and when other acids are selected, the solubility of the phenol sulfonophthalein is lower, which affects the reaction effect;

[0032] If the proportion of the selected organic carboxylic acid is too low, the acidification is not sufficient, and if the proportion is too high, the reagent is wasted; it is good that the volume of the selected water is equivalent to the volume of the acid;

[0033] For the bromination reaction, the selected liquid bromine is at least 2 equivalents of phenol sulfonophthalein, which is far lower than at least 4 equivalents in the prior art, thereby saving a large amount of liquid bromine;

[0034] The hydrogen peroxide used in the oxidation reaction is at least 2 times the amount of phenol sulfonphthalein, that is, at least 1 times the amount of liquid bromine, which can be fully oxidized;

[0035] The temperature of the temperature control reaction is lower than 25 DEG C, the reaction is too slow, the reaction temperature is higher than 70 DEG C, which can easily cause side reactions, and affect the yield and purity.

[0036] Further, the application provides a preparation method of the tetrabromophenol tetrahalosulfonphthalein, in the oxidation and bromination step: the mass-volume ratio of the 3,4,5,6-tetrahalophenol sulfonphthalein to the added organic carboxylic acid is 1g:1-12mL; the organic carboxylic acid is one of formic acid, acetic acid or propionic acid; the mass-volume ratio of the 3,4,5,6-tetrahalophenol sulfonphthalein to the added water is 1:1-1:12; the molar ratio of the 3,4,5,6-tetrabromophenol sulfonphthalein to the added liquid bromine is 1:2-1:3; the molar ratio of the hydrogen peroxide to the 3,4,5,6-tetrahalophenol sulfonphthalein is 1:1-1:6; the molar ratio of the hydrogen peroxide to the liquid bromine is 1:1-1:2; the temperature control reaction temperature is 20 DEG C-70 DEG C; and the temperature control reaction time is 1-12 hours;

[0037] In the oxidation and bromination step of the application, the amount of liquid bromine used in bromination is saved by more than 50% compared with the prior art; the purity of the starting material 3,4,5,6-tetrahalophenol sulfonphthalein is 90%, the yield of the crude tetrabromophenol tetrahalosulfonphthalein prepared by oxidation and bromination is 92%, and the purity is 93%;

[0038] The experimental results of the salt formation and purification step of the application show that:

[0039] When the selected base salt is a carbonate salt, the reaction system will be too dark due to the strong basicity; when the selected base is an acetate salt, the reaction time will be too long and the reaction will not be complete due to the weak basicity; when the selected base is a bicarbonate salt, the basicity is moderate, which is just fast and complete reaction; if the amount of the selected base is too small, that is, less than 1 eq, the reaction will not be complete, which will affect the yield; if the amount of the selected base is too much, that is, more than 1.5 eq, there will be residual base which is not easy to remove, which will affect the purity; the amount of the selected base is preferably 1-1.5 eq, and the reaction effect is better;

[0040] When the solvent selected for the salt formation reaction is a protic solvent, the reaction cannot be completely reacted, and the tetrabromophenol tetrahalosulfonphthalein will also cause color reaction, resulting in too dark product; when aprotic solvent is selected, the reaction can be completely reacted, and the color is lighter; the aprotic solvent can be any one of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether and isobutyl ether;

[0041] The reaction is not sufficient, the purity is low when the volume of the aprotic solvent is too small compared with the crude product of tetrabromophenol tetrahalosulfonophthalein; the yield is low when the volume of the aprotic solvent is too large compared with the crude product of tetrabromophenol tetrahalosulfonophthalein; the mass-volume ratio of the crude product of tetrabromophenol tetrahalosulfonophthalein to the aprotic solvent is 1:1-1:12, the yield is higher, the purity is higher, and the effect is better;

[0042] The reaction rate is too slow, the reaction time is too long, and the reaction efficiency is low when the reaction temperature is lower than 30 DEG C; the side reaction is easily caused, and the color of the product is deepened when the reaction temperature is higher than 70 DEG C;

[0043] The reaction is not complete, the yield is low, the purity is low, and the free impurities are high when the reaction time is less than 2 hours; the reaction time is too long, the side reaction is more, the impurities are high, and the purity is low when the reaction time is more than 10 hours;

[0044] After the salt formation reaction, the alkali metal salt of tetrabromophenol tetrahalosulfonophthalein mainly contains three kinds of substances: the first kind is the macromolecule after salt formation, that is, the salt of tetrabromophenol tetrahalosulfonophthalein, the second kind is the small molecule which cannot be salted, and the third kind is the small molecule which can be salted; after the salt formation reaction, the salt formation solvent is used to realize once crystallization, the small molecule which is salted and the small molecule which is not salted are all dissolved in the crystallization mother liquor, and the salt of tetrabromophenol tetrahalosulfonophthalein is difficult to dissolve in the crystallization solvent, so that the separation of the product and the impurities is realized, and the purification effect is achieved.

[0045] Further, the application provides a preparation method of tetrabromophenol tetrahalosulfonophthalein, in the salt formation and purification step: the dosage of the alkali metal salt is 1.0-1.5 eq of tetrabromophenol tetrahalosulfonophthalein; the selected alkali metal salt is bicarbonate, preferably lithium bicarbonate, sodium bicarbonate or potassium bicarbonate; the mass-volume ratio of the crude product of tetrabromophenol tetrahalosulfonophthalein to the aprotic solvent is 1 g:2-12 mL; the aprotic solvent is any one of acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether, benzene, toluene and xylene; the temperature-controlled reaction is 30 DEG C-70 DEG C; and the reaction time is 1-12 hours;

[0046] In the salt formation and purification step, the yield of the alkali metal salt of tetrabromophenol tetrahalosulfonophthalein prepared by the salt formation reaction and the self reaction system crystallization is 93%, and the purity is 97.0%;

[0047] The experimental results in the acid conversion purification step show that:

[0048] The acid selected for the acid conversion of the present application is other acid, which affects the stability of the product and reduces the purity; the selected organic carboxylic acid is one of formic acid, acetic acid or propionic acid, and when other organic carboxylic acid is selected, the purity is lower after recrystallization; when the amount of the organic carboxylic acid added is 1 equivalent, the acidification is insufficient and the yield is lower, and when the molar ratio of the tetrabromophenol tetrahalosulfonophthalein to the added organic carboxylic acid is 1:1 to 1:3, the yield is higher, the purity is higher, and the effect is better;

[0049] The purification in the acid conversion purification process of the present application is realized by recrystallization in an organic acid aqueous solution; in the recrystallization process, a small amount of polar molecule impurities are dissolved in the organic acid aqueous solution, and the tetrabromophenol tetrahalosulfonophthalein is difficult to dissolve in the organic acid aqueous solution, so that the tetrabromophenol tetrahalosulfonophthalein is purified again;

[0050] In the acid conversion purification process, the volume of water is too small, the stirring and acidification are not sufficient, the yield is reduced, and the purity is reduced, and when the volume of water is too large, the product is dissolved in the solution, which affects the yield, the mass / volume ratio of the tetrabromophenol tetrahalosulfonophthalein to the added water is 1:2 to 1:10, the yield is higher, the purity is higher, and the effect is better; the temperature control reaction temperature is lower than 35℃, the acidification reaction time is too long, the recrystallization effect is reduced, the yield is lower, and the purity is lower, and when the temperature control reaction temperature is higher than 75℃, the purity and yield are reduced, the temperature control reaction temperature is 35℃ to 70℃; the temperature control reaction time is 1 to 10 hours, the yield is higher, the purity is higher, and the effect is better;

[0051] Further, the present application provides a preparation method of tetrabromophenol tetrahalosulfonophthalein, and in the acid conversion purification step: the molar ratio of the tetrabromophenol tetrahalosulfonophthalein to the added organic carboxylic acid is 1:1 to 1:6; the organic carboxylic acid is one of formic acid, acetic acid or propionic acid; the mass / volume ratio of the tetrabromophenol tetrahalosulfonophthalein to the added water is 1:1 to 1:12; and the temperature control reaction temperature is 35℃ to 90℃; and the temperature control reaction time is 1 to 12 hours;

[0052] In the acid conversion purification step of the present application, through the acid conversion reaction and using the self-reaction system recrystallization, the yield of the prepared tetrabromophenol tetrahalosulfonophthalein is 94%, and the purity is 99.0%;

[0053] Further, the application provides a preparation method of tetrabromophenol tetrahalosulfonphthalein, in the oxidation bromination step, the mass-volume ratio of 3,4,5,6-tetrahalophenol sulfonphthalein to carboxylic acid is 1:2-1:6; the mass-volume ratio of 3,4,5,6-tetrahalophenol sulfonphthalein to water is 1:2-1:6; the molar ratio of 3,4,5,6-tetrabromophenol sulfonphthalein to liquid bromine is 1:2-1:3; the molar ratio of hydrogen peroxide to 3,4,5,6-tetrahalophenol sulfonphthalein is 1:1-1:6; the molar ratio of hydrogen peroxide to liquid bromine is 1:1-1:2; the temperature of the controlled temperature reaction is 25-60 DEG C; and the controlled temperature reaction time is 1-6 hours.

[0054] In the salt formation purification step, the mass-volume ratio of tetrabromophenol tetrahalosulfonphthalein crude product to aprotic solvent is 1:2-1:6; the aprotic solvent is one of acetone, acetonitrile, dioxane, ethyl acetate or dichloromethane; the temperature of the controlled temperature reaction is 35-65 DEG C; and the reaction time is 1-6 hours.

[0055] In the acid conversion purification step, the molar ratio of tetrabromophenol tetrahalosulfonphthalein salt to organic carboxylic acid is 1:2-1:4; the mass-volume ratio of tetrabromophenol tetrahalosulfonphthalein salt to water is 1:2-1:6; the temperature of the controlled temperature reaction is 40-70 DEG C; and the controlled temperature reaction time is 1-6 hours.

[0056] The application completes the first purification through oxidation bromination, the second purification through crystallization of the aprotic solvent used in salt formation, and the third purification through recrystallization of the carboxylic acid aqueous solution used in acid conversion, so that the purity of the finally prepared tetrabromophenol tetrahalosulfonphthalein alkali metal salt product is more than 80% in total yield and more than 99.0% in purity.

[0057] Further, the application provides a preparation method of tetrabromophenol tetrahalosulfonphthalein, which improves the reaction efficiency through oxidation bromination, greatly reduces the amount of liquid bromine used to reduce the cost and improve the yield, improves the purity of tetrabromophenol tetrahalosulfonphthalein salt through salt formation purification, and further improves the purity of tetrabromophenol tetrahalosulfonphthalein and the total yield through acid conversion purification.

[0058] Compared with the prior art, the application provides a preparation method of tetrabromophenol tetrahalosulfonphthalein with the following beneficial effects:

[0059] The application provides a preparation method of tetrabromophenol tetrahalosulfonphthalein, which has high yield, high purity and low cost, is simple, mild and beneficial to mass production, and is suitable for wide promotion and application. DETAILED DESCRIPTION

[0060] The technical solutions of the present application will be clearly and completely described below through specific embodiments. Apparently, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application.

[0061] Example 1: Comparison of implementation effects in oxidation and bromination process

[0062] (1) Selection of acid

[0063] 3,4,5,6-tetrabromophenol sulfonaphthol 70.0 grams (0.1 moL, purity 90.12%, same below) was weighed in five portions, and formic acid, acetic acid, propionic acid, butyric acid and hydrochloric acid were added in a mass-volume ratio of 1:3, respectively, and heated and stirred at 60°C until uniform; water was added in the same mass-volume ratio, and cooled to room temperature; 2.2 eq of hydrogen peroxide was added and stirred uniformly; 2.2 eq of liquid bromine was added and stirred, and the temperature was controlled at 40°C for 2 hours; after the reaction was completed, the reaction liquid was cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrabromosulfonaphthol crude product, and the relevant experimental data are shown in Table I:

[0064] Table I

[0065]

[0066] The data in Table I show that the yield and purity using formic acid, acetic acid or propionic acid are significantly higher than those using butyric acid or hydrochloric acid; it can be seen that the implementation effect of formic acid, acetic acid or propionic acid is better.

[0067] (2) Selection of acid feeding ratio

[0068] 3,4,5,6-tetrabromophenol sulfonaphthol 70.0 grams (0.1 moL) was weighed in five portions, and acetic acid was added in a mass-volume ratio of 1:1, 1:2, 1:3, 1:6 and 1:7, respectively, and heated and stirred at 50°C until uniform; water was added in a mass-volume ratio of 1:3, and cooled to room temperature; 2.2 eq of hydrogen peroxide was added and stirred uniformly; 2.2 eq of liquid bromine was added and stirred, and the temperature was controlled at 40°C for 2 hours; after the reaction was completed, the reaction liquid was cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrabromosulfonaphthol crude product, and the relevant experimental data are shown in Table II:

[0069] Table II

[0070]

[0071] The data in Table II show that when the feeding ratio of acetic acid is lower than 1:2 or higher than 1:7, the yield and purity decrease; when the feeding ratio of acetic acid is 1:2 to 1:6, the yield and purity are higher, and the implementation effect is better.

[0072] (3) Selection of water addition ratio

[0073] Weigh 70.0 grams (0.1 moL) of 3,4,5,6-tetrabromophenol sulfone phthalein, and add acetic acid in a mass-volume ratio of 1:2 for each of the five portions, and heat and stir at 50°C until uniform. Add water in the same mass-volume ratio, and add acetic acid in a mass-volume ratio of 1:1, 1:2, 1:3, 1:6, and 1:7, respectively, and cool to room temperature. Add 2.2 eq of hydrogen peroxide, and stir until uniform. Add 2.2 eq of liquid bromine, and stir while controlling the temperature at 40°C for 2 hours. After the reaction is complete, cool the reaction liquid to room temperature, filter, collect the filter cake, and dry to obtain crude tetrabromophenol tetrabromosulfone phthalein. The relevant experimental data are shown in Table III:

[0074] Table III

[0075]

[0076] The data in Table III show that when the water addition ratio is less than 1:1 or more than 1:6, the yield and purity decrease. When the water addition ratio is between 1:2 and 1:6, the yield and purity are higher, and the implementation effect is better.

[0077] (4) Selection of liquid bromine dosage

[0078] Weigh 70.0 grams (0.1 moL) of 3,4,5,6-tetrabromophenol sulfone phthalein, and add acetic acid in a mass-volume ratio of 1:2 for each of the five portions, and heat and stir at 50°C until uniform. Add water in a mass-volume ratio of 1:2, and cool to room temperature. Add 3.2 eq of hydrogen peroxide, and stir until uniform. Add 1.5, 2.0, 2.5, 3.0, and 3.5 eq of liquid bromine, and stir while controlling the temperature at 40°C for 2 hours. After the reaction is complete, cool the reaction liquid to room temperature, filter, collect the filter cake, and dry to obtain crude tetrabromophenol tetrabromosulfone phthalein. The relevant experimental data are shown in Table IV:

[0079] Table IV

[0080]

[0081]

[0082] The data in Table IV show that when the liquid bromine dosage is 1.5 eq, the yield and purity are low. When the liquid bromine dosage is 2.0 eq or more, the purity and yield are both significantly higher than when the dosage is 1.5 eq, but the yield and purity do not increase significantly compared to when the dosage is 2.0 eq. When the liquid bromine dosage is 3.5 eq, the yield does not increase, and the purity begins to decrease. Therefore, the implementation effect is better when the liquid bromine dosage is between 2.0 eq and 3.0 eq.

[0083] (5) Selection of hydrogen peroxide dosage

[0084] Weigh 3,4,5,6-tetrabromophenol sulfonaphthol 70.0 grams (0.1 moL), respectively, 5 parts, according to the mass volume ratio of 1:2 acetic acid, 50 ℃ heating stirring to uniform; According to the mass volume ratio of 1:2 water, cooling to room temperature; 2.5 eq hydrogen peroxide, stirring uniform; 2.0 eq of liquid bromine, stirring, temperature control 20 ℃, 25 ℃, 40 ℃, 60 ℃, 65 ℃ reaction 1-6 hours, detection reaction, after the reaction, the reaction liquid cooling to room temperature, filtration, filter cake collection, drying, tetrabromophenol tetrabromophenol sulfonaphthol crude product, the relevant experimental data are shown in table VI:

[0085] Table V

[0086]

[0087] The data in table V show that: hydrogen peroxide feeding 1.5 equivalents is too small, can not completely oxidize hydrogen bromide to generate liquid bromine to participate in bromination reaction, low yield, low purity; hydrogen peroxide feeding amount is more than 2.0 equivalents, compared with 1.5 equivalents, the purity and yield are obviously increased, when the hydrogen peroxide feeding reaches 6.0 equivalents, the yield and purity compared with 2.0 equivalents, there is no obvious increase; Liquid bromine feeding is 6.5 equivalents, the yield decreases slightly, the purity decreases slightly; It can be seen that the implementation effect is better when the hydrogen peroxide feeding is between 2.0 and 6.0 equivalents;

[0088] (6) Selection of reaction temperature and time

[0089] Weigh 3,4,5,6-tetrabromophenol sulfonaphthol 70.0 grams (0.1 moL), respectively, 5 parts, according to the mass volume ratio of 1:2 acetic acid, 50 ℃ heating stirring to uniform; According to the mass volume ratio of 1:2 water, cooling to room temperature; 2.5 eq hydrogen peroxide, stirring uniform; 2.0 eq of liquid bromine, stirring, temperature control 20 ℃, 25 ℃, 40 ℃, 60 ℃, 65 ℃ reaction 1-6 hours, detection reaction, after the reaction, the reaction liquid cooling to room temperature, filtration, filter cake collection, drying, tetrabromophenol tetrabromophenol sulfonaphthol crude product, the relevant experimental data are shown in table VI:

[0090] Table VI

[0091]

[0092] The data in table VI show that: the reaction temperature is 20 ℃, the reaction time is 6 hours, the yield is low, the purity is low, the reaction time is too long; The reaction temperature is 60 ℃, the reaction time is 1 hour, although the time is short, but the reaction is too violent, the byproduct is more, the yield and purity are decreased; The reaction temperature is 25 ℃-60 ℃, the reaction time is 1-6 hours, the reaction yield is high, the purity is high, the implementation effect is better;

[0093] Example 2: Comparison of implementation effects in salt formation and purification process

[0094] 1) 3,4,5,6-tetrabromophenol sulfone phthalein 2100 grams (3.0 moL) was weighed, 4200 mL of acetic acid was added according to the mass-volume ratio of 1:2, heated and stirred at 60°C until uniform, 4200 mL of water was added, cooled to room temperature, 7.5 moL of hydrogen peroxide was added, stirred uniformly, 959 grams of liquid bromine (6.0 moL) was added, stirred, controlled temperature 45°C, reacted for 2 hours; after the reaction was completed, the reaction liquid was cooled to room temperature, filtered, the filter cake was collected and dried to obtain 2800 grams of tetrabromophenol tetrabromosulfone phthalein crude product, the yield was 94.7%, and the purity was 93.15%, which was used in the following experiments;

[0095] (1) Selection of base salt

[0096] The tetrabromophenol tetrabromosulfone phthalein crude product obtained in the above step was weighed in 5 parts, each 98.6 grams (0.1 moL), and acetonitrile was added according to the mass-volume ratio of 1:4, respectively. 1.1 ep lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, sodium carbonate and sodium acetate were added, stirred, controlled temperature 50°C, reacted for 4 hours; after the reaction was completed, crystallization was carried out in the reaction liquid, cooled to room temperature, filtered, the filter cake was collected and dried to obtain the corresponding salt of tetrabromophenol tetrabromosulfone phthalein, and the relevant experimental data are shown in Table VII:

[0097] Table VII

[0098]

[0099] The data in Table VII show that: the base salt is sodium carbonate, which is too basic, the side reaction increases, the yield is low, and the purity is low; the base salt is sodium acetate, which is too weakly basic, the reaction is slow, the yield is low, and the purity is low; the base salt is lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, the yield is high, the purity is high, and the implementation effect is better;

[0100] (2) Selection of base salt feeding equivalent

[0101] The tetrabromophenol tetrabromosulfone phthalein crude product obtained in the above step was weighed in 5 parts, each 98.6 grams (0.1 moL), and acetonitrile was added according to the mass-volume ratio of 1:4, respectively. 0.9, 1.0, 1.1, 1.5, 1.6 ep sodium bicarbonate was added, stirred, controlled temperature 50°C, reacted for 4 hours; after the reaction was completed, crystallization was carried out in the reaction liquid, cooled to room temperature, filtered, the filter cake was collected and dried to obtain the corresponding salt of tetrabromophenol tetrabromosulfone phthalein, and the relevant experimental data are shown in Table VIII:

[0102] Table VIII

[0103]

[0104]

[0105] The data in Table VIII show that when the amount of base salt is 0.9 equivalent, the reaction yield is low and the purity is slightly low; when the amount of base salt is 1.6 equivalent, the side reaction increases, the yield is low, and the purity is low; when the amount of base salt is 1 to 1.5 equivalent, the yield is high, the purity is high, and the implementation effect is good;

[0106] (3) Selection of salt forming solvent

[0107] The crude tetrabromophenol tetrabromothio-phthalate obtained in the previous step was weighed in 6 portions, each 98.6 grams (0.1 moL), and acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, or any other solvent was added in a mass-volume ratio of 1:4, and 1.1 ep of sodium bicarbonate was added, stirring, controlling the temperature at 50°C for 4 hours; after the reaction was completed, crystallization was carried out in the reaction liquid, cooled to room temperature, filtered, collected the filter cake, and dried to obtain tetrabromophenol tetrabromothio-phthalate sodium salt. The relevant experimental data are shown in Table IX:

[0108] Table IX

[0109]

[0110] The data in Table IX show that when any other solvent is selected as the salt forming solvent, the yield is low and the purity is low; when acetone, acetonitrile, dioxane, ethyl acetate, or dichloromethane is selected, the yield is high and the purity is high, and the implementation effect is good;

[0111] (4) Selection of salt forming solvent dosage ratio

[0112] The crude tetrabromophenol tetrabromothio-phthalate obtained in the previous step was weighed in 5 portions, each 98.6 grams (0.1 moL), and acetonitrile was added in a mass-volume ratio of 1:1, 1:2, 1:4, 1:6, and 1:7, and 1.1 ep of sodium bicarbonate was added, stirring, controlling the temperature at 50°C for 4 hours; after the reaction was completed, crystallization was carried out in the reaction liquid, cooled to room temperature, filtered, collected the filter cake, and dried to obtain tetrabromophenol tetrabromothio-phthalate sodium salt. The relevant experimental data are shown in Table X:

[0113] Table X

[0114]

[0115] The data in Table X show that when the mass-volume ratio of the salt forming solvent is 1:1, the reaction is not sufficient, the yield is low, and the purity is low; when the mass-volume ratio is 1:7, the system is too large, the yield is low, and solvent is wasted; when the mass-volume ratio is selected in the range of 1:2 to 1:6, the yield is high, the purity is high, and the implementation effect is good;

[0116] (5) Selection of salt forming reaction temperature and time

[0117] The crude tetrabromophenol tetrabromothio-phthalate obtained in the previous step was weighed in 5 portions, 98.6 grams (0.1 moL) each, and acetonitrile was added in a mass-volume ratio of 1:3, 1.1 ep of sodium bicarbonate was added, and stirring was performed, and the temperature was controlled at 30, 35, 55, 65, and 70°C, respectively; after the reaction was completed, crystallization was performed in the reaction liquid, and the temperature was cooled to room temperature, and the filter cake was collected by filtration and dried to obtain tetrabromophenol tetrabromothio-phthalate sodium salt, and the relevant experimental data are shown in Table XI:

[0118] Table XI

[0119]

[0120]

[0121] The data in Table XI show that when the reaction temperature is 30°C and the reaction time is 6 hours, the temperature is too low and the time is too long, the yield is low and the purity is low; when the reaction temperature is 70°C and the reaction time is 1 hour, the temperature is too high, the side reaction increases, the yield is low, and the purity is low; when the reaction temperature is 35 to 65°C and the reaction time is 1-6 hours, the yield is high, the purity is high, and the implementation effect is better;

[0122] Example 3: Comparison of implementation effects in the acid conversion and purification process

[0123] 1) 1) 3,4,5,6-tetrabromophenol thio-phthalate 2100 grams (3.0 moL) was weighed, acetic acid 4200 mL was added in a mass-volume ratio of 1:2, heating and stirring was performed at 60°C until uniform, water 4200 mL was added, the temperature was cooled to room temperature, 7.5 moL of hydrogen peroxide was added, stirring was performed until uniform, 959 grams of liquid bromine (6.0 moL) was added, stirring was performed, the temperature was controlled at 45°C, and the reaction was performed for 2 hours; after the reaction was completed, the reaction liquid was cooled to room temperature, filtration was performed, the filter cake was collected, and drying was performed to obtain 2782 grams of crude tetrabromophenol tetrabromothio-phthalate, the yield was 94.1%, and the purity was 94.46%, which was used in the following experiments;

[0124] 2) The crude tetrabromophenol tetrabromothio-phthalate obtained in the previous step was weighed in 5 portions, 98.6 grams (0.1 moL) each, and acetonitrile was added in a mass-volume ratio of 1:3, 1.1 ep of sodium bicarbonate was added, and stirring was performed, and the temperature was controlled at 30, 35, 55, 65, and 70°C, respectively; after the reaction was completed, crystallization was performed in the reaction liquid, and the temperature was cooled to room temperature, and the filter cake was collected by filtration and dried to obtain tetrabromophenol tetrabromothio-phthalate sodium salt, and the relevant experimental data are shown in Table XI:

[0125] (1) Selection of acid

[0126] Weighed four bromophenol four bromosulfonothal sodium salt 5 parts, each 100.7 grams (0.1 moL), according to a certain mass volume ratio 1:4 water, according to 2.0 eq organic carboxylic acid, stirring, temperature control 55℃ reaction 2 hours; after the reaction, recrystallization in the reaction liquid, cooled to room temperature, filtration, collection of filter cake, drying, prepared four bromophenol four bromosulfonothal pure product, see table XII:

[0127] Table XII

[0128]

[0129] Data in table XII shows that: using formic acid, acetic acid or propionic acid three kinds of organic carboxylic acid, yield and purity are significantly higher than butyric acid or hydrochloric acid; it can be seen that formic acid, acetic acid or propionic acid three kinds of organic carboxylic acid implementation effect is better.

[0130] (2) the selection of organic carboxylic acid feeding equivalent

[0131] Weighed four bromophenol four bromosulfonothal sodium salt 5 parts, each 100.7 grams (0.1 moL), respectively according to a certain mass volume ratio 1:4 water, respectively according to 1.5 eq, 2.0 eq, 3.0 eq, 4.0 eq, 4.5 eq acetic acid, stirring, temperature control 55℃ reaction 2 hours; after the reaction, recrystallization in the reaction liquid, cooled to room temperature, filtration, collection of filter cake, drying, prepared four bromophenol four bromosulfonothal pure product, see table XIII:

[0132] Table XIII

[0133]

[0134] Data in table XIII shows that: acetic acid feeding ratio 1.0 equivalent, due to insufficient acidification, yield is too low, the purity is not improved; acetic acid feeding ratio is 4.5 equivalent, acid solution appears, the yield is reduced; when acetic acid feeding ratio is 2.0-4.0 equivalent, the yield is higher, the purity is higher, the implementation effect is better;

[0135] (3) the selection of water feeding ratio

[0136] Weighed four bromophenol four bromosulfonothal sodium salt 5 parts, each 100.7 grams (0.1 moL), respectively according to a certain mass volume ratio 1:1, 1:2, 1:3, 1:6, 1:7 water, respectively according to 1.1 eq acetic acid, stirring, temperature control 55℃ reaction 2 hours; after the reaction, recrystallization in the reaction liquid, cooled to room temperature, filtration, collection of filter cake, drying, prepared four bromophenol four bromosulfonothal pure product, see table XIV:

[0137] Table XIV

[0138]

[0139] The data in Table XIV show that when the water feeding ratio is 1:1, the acidification is insufficient, the yield is low, and the purity is not improved; when the water feeding ratio is 1:7, the yield is too low; when the water feeding ratio is 1:2 to 1:6, the yield is relatively high, the purity is relatively high, and the implementation effect is relatively good;

[0140] (4) Selection of acidification temperature and time

[0141] 5 parts of the tetrabromophenol tetrahalophthalide sodium salt prepared in the previous step, each weighing 100.7 g (0.1 mol), were weighed, water was added in a certain mass-volume ratio of 1:3, and acetic acid was added in an amount of 1.1 eq, respectively, and the reaction was stirred and temperature-controlled; after the reaction was completed, the reaction liquid was recrystallized, cooled to room temperature, filtered, the filter cake was collected and dried to obtain pure tetrabromophenol tetrabromophthalide, and the relevant experimental data are shown in Table XV:

[0142] Table XV

[0143]

[0144]

[0145] The data in Table XV show that when the reaction temperature is 35°C and the reaction time is 6 hours, the temperature is too low and the time is too long, the acidification is insufficient, the yield is low, and the purity is reduced; when the reaction temperature is 75°C and the reaction time is 1 hour, the temperature is too high, the side reactions increase, the yield is low, and the purity is low; when the reaction temperature is 40-70°C and the reaction time is 1-6 hours, the yield is high, the purity is high, and the implementation effect is relatively good;

[0146] Example 4: Preparation of tetrabromophenol tetrachlorophthalide

[0147] 1) 49.2 g of 3,4,5,6-tetrachlorophenol phthalide was weighed and added to acetic acid 150 mL, heated and stirred at 45°C until homogeneous; 150 mL of pure water was added and cooled to room temperature; 29 mL (35%) of hydrogen peroxide was added and stirred uniformly; then 40.0 g of liquid bromine was slowly added dropwise, stirred, and temperature-controlled at 55°C for 5 h; after the reaction was completed, the reaction liquid was cooled to room temperature, filtered, the filter cake was collected and dried to obtain 76.5 g of tetrabromophenol tetrachlorophthalide crude product, with a yield of 94.7% and a purity of 93.45%;

[0148] 2) 76.5 g of the tetrabromophenol tetrachlorophthalide crude product prepared in the previous step was added to acetonitrile 300 mL, and then 7.0 g of lithium bicarbonate was added, stirred, and temperature-controlled at 45°C for 5 hours; after the reaction was completed, the reaction liquid was crystallized, cooled to room temperature, filtered, the filter cake was collected and dried to obtain 72.4 g of tetrabromophenol tetrachlorophthalide lithium salt, with a yield of 93.9% and a purity of 97.71%;

[0149] 3) Take 72.4 g of the tetrabromophenol tetrachlorothiophthalimide lithium salt prepared in the previous step, add 200 mL of water, add 10.8 mL of acetic acid, stir, control the temperature at 55°C for 4 hours; after the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, dry, and prepare 66.7 g of pure tetrabromophenol tetrachlorothiophthalimide, with a yield of 92.8%, a total yield of 82.6%, and a purity of 99.17%;

[0150] Example 5: Preparation of tetrabromophenol tetrachlorothiophthalimide

[0151] 1) Weigh 49.2 g of 3,4,5,6-tetrachlorophenol sulfone phthalimide, add 100 mL of acetic acid, heat and stir at 60°C until homogeneous; add 100 mL of pure water, cool to room temperature; add 30 mL (35%) of hydrogen peroxide, stir until homogeneous; then slowly drop in 38.5 g of liquid bromine, stir, control the temperature at 45°C for 4 hours; after the reaction is completed, cool the reaction solution to room temperature, filter, collect the filter cake, dry, and prepare 76.2 g of crude tetrabromophenol tetrachlorothiophthalimide, with a yield of 94.3% and a purity of 93.58%.

[0152] 2) Take 76.2 g of the crude tetrabromophenol tetrachlorothiophthalimide prepared in the previous step, add 300 mL of acetonitrile, then add 8.5 g of sodium bicarbonate, stir, control the temperature at 55°C for 3 hours; after the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, dry, and prepare 73.0 g of tetrabromophenol tetrachlorothiophthalimide sodium salt, with a yield of 93.2% and a purity of 97.15%.

[0153] 3) Take 73.0 g of the tetrabromophenol tetrachlorothiophthalimide sodium salt prepared in the previous step, add 170 mL of water, add 10.6 mL of acetic acid, stir, control the temperature at 55°C for 2 hours; after the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, dry, and prepare 65.9 g of pure tetrabromophenol tetrachlorothiophthalimide, with a yield of 92.8%, a total yield of 81.6%, and a purity of 99.32%.

[0154] Example 6: Preparation of tetrabromophenol tetrachlorothiophthalimide

[0155] 1) Weigh 49.2 g of 3,4,5,6-tetrachlorophenol sulfone phthalimide, add 200 mL of acetic acid, heat and stir at 55°C until homogeneous; add 200 mL of pure water, cool to room temperature; add 28 mL (35%) of hydrogen peroxide, stir until homogeneous; then slowly drop in 38.4 g of liquid bromine, stir, control the temperature at 55°C for 4 hours; after the reaction is completed, cool the reaction solution to room temperature, filter, collect the filter cake, dry, and prepare 75.9 g of crude tetrabromophenol tetrachlorothiophthalimide, with a yield of 94.0% and a purity of 93.72%.

[0156] 2) Add 75.9 g of the crude tetrabromophenol tetrachlorothiophenol prepared in the previous step into 350 mL of acetone, and then add 9.5 g of potassium bicarbonate, stir, and control the temperature at 55°C for 4 hours. After the reaction is completed, crystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, and dry to obtain 74.4 g of tetrabromophenol tetrachlorothiophenol potassium salt, with a yield of 93.5% and a purity of 97.74%.

[0157] 3) Add 74.4 g of the tetrabromophenol tetrachlorothiophenol potassium salt prepared in the previous step into 300 mL of water, and then add 10.6 mL of formic acid, stir, and control the temperature at 55°C for 2 hours. After the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, and dry to obtain 65.8 g of tetrabromophenol tetrachlorothiophenol, with a yield of 92.6%, a total yield of 81.5%, and a purity of 99.12%.

[0158] Example 7: Preparation of tetrabromophenol tetrabromothiophenol

[0159] 1) Weigh 70.0 g of 3,4,5,6-tetrabromophenol sulfonephthalein, add 350 mL of acetic acid, and heat and stir at 45°C until homogeneous; add 350 mL of pure water, and cool to room temperature; add 29 mL (35%) of hydrogen peroxide, and stir until homogeneous; then slowly drop in 40 g of liquid bromine, stir, control the temperature at 55°C for 5 hours, and cool the reaction solution to room temperature after the reaction is completed. Filter, collect the filter cake, and dry to obtain 91.5 g of tetrabromophenol tetrabromothiophenol, with a yield of 92.8% and a purity of 93.62%.

[0160] 2) Add 91.5 g of the crude tetrabromophenol tetrabromothiophenol prepared in the previous step into 400 mL of acetonitrile, and then add 7.0 g of lithium bicarbonate, stir, and control the temperature at 45°C for 5 hours. After the reaction is completed, crystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, and dry to obtain 85.8 g of tetrabromophenol tetrabromothiophenol lithium salt, with a yield of 93.2% and a purity of 97.57%.

[0161] 3) Add 85.8 g of the tetrabromophenol tetrabromothiophenol lithium salt prepared in the previous step into 300 mL of water, and then add 10.4 mL of acetic acid, stir, and control the temperature at 55°C for 4 hours. After the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, and dry to obtain 80.7 g of tetrabromophenol tetrabromothiophenol, with a yield of 94.6%, a total yield of 81.9%, and a purity of 99.27%.

[0162] Example 8: Preparation of tetrabromophenol tetrabromothiophenol

[0163] 1) Weigh 70.0 g of 3,4,5,6-tetrabromophenol sulfone phthalein, add acetic acid 200 mL, heat and stir at 45 °C until homogeneous; add pure water 200 mL, cool to room temperature; add 28 mL (35%) hydrogen peroxide, stir until homogeneous; then slowly drop in 39 g of liquid bromine, stir, control temperature at 45 °C for 5 h; after the reaction is completed, cool the reaction liquid to room temperature, filter, collect the filter cake, dry, to obtain 92.8 g of tetrabromophenol tetrabromosulfone phthalein crude product, yield 94.2%, purity 93.9%.

[0164] 2) Add 92.8 g of tetrabromophenol tetrabromosulfone phthalein crude product prepared in the previous step to acetonitrile 400 mL, then add 9.5 g of sodium bicarbonate, stir, control temperature at 45 °C for 5 h; after the reaction is completed, crystallize in the reaction liquid, cool to room temperature, filter, collect the filter cake, dry, to obtain 88.5 g of tetrabromophenol tetrabromosulfone sodium salt, yield 93.1%, purity 97.5%;

[0165] 3) Add 88.5 g of tetrabromophenol tetrabromosulfone sodium salt prepared in the previous step to 500 mL of water, add 10.6 mL of acetic acid, stir, control temperature at 60 °C for 6 h; after the reaction is completed, recrystallize in the reaction liquid, cool to room temperature, filter, collect the filter cake, dry, to obtain 81.8 g of tetrabromophenol tetrabromosulfone pure product, yield 94.5%, total yield 83.0%, purity 99.52%;

[0166] Example 9: Preparation of tetrabromophenol tetrabromosulfone phthalein

[0167] 1) Weigh 70.0 g of 3,4,5,6-tetrabromophenol sulfone phthalein, add acetic acid 200 mL, heat and stir at 45 °C until homogeneous; add pure water 200 mL, cool to room temperature; add 28 mL (35%) hydrogen peroxide, stir until homogeneous; then slowly drop in 39 g of liquid bromine, stir, control temperature at 45 °C for 5 h; after the reaction is completed, cool the reaction liquid to room temperature, filter, collect the filter cake, dry, to obtain 92.8 g of tetrabromophenol tetrabromosulfone phthalein crude product, yield 94.2%, purity 93.9%.

[0168] 2) Add 92.8 g of tetrabromophenol tetrabromosulfone phthalein crude product prepared in the previous step to acetonitrile 400 mL, then add 9.5 g of sodium bicarbonate, stir, control temperature at 45 °C for 5 h; after the reaction is completed, crystallize in the reaction liquid, cool to room temperature, filter, collect the filter cake, dry, to obtain 88.5 g of tetrabromophenol tetrabromosulfone sodium salt, yield 93.1%, purity 97.5%;

[0169] 3) Take the tetrabromophenol tetrabromothiolate potassium salt 88.3 g prepared in the previous step, add 360 mL of water, add 10.4 mL of propionic acid, stir, control the temperature at 50°C for 6 hours; after the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, dry, and prepare 79.7 grams of pure tetrabromophenol tetrabromothiolate, with a yield of 93.8%, a total yield of 80.9%, and a purity of 99.41%.

[0170] Example 10: Preparation of tetrabromophenol tetraiodothiolate

[0171] 1) Weigh 3,4,5,6-tetraiodophenol thiolate 85.8 g, add acetic acid 400 mL, heat and stir to uniformity at 45°C; add pure water 400 mL, cool to room temperature; add 30 mL (35%) hydrogen peroxide, stir evenly; then slowly drop in 38 g of liquid bromine, stir, control the temperature at 55°C for 5h; after the reaction is completed, cool the reaction solution to room temperature, filter, collect the filter cake, dry, and prepare 110.5 g of tetrabromophenol tetraiodothiolate crude product, with a yield of 94.1% and a purity of 93.46%.

[0172] 2) Take the tetrabromophenol tetraiodothiolate crude product 110.5 g prepared in the previous step, add acetonitrile 400 mL, then add 6.6 g of lithium bicarbonate, stir, control the temperature at 45°C for 5 hours; after the reaction is completed, crystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, dry, and prepare 103.8 g of tetrabromophenol tetraiodothiolate lithium salt, with a yield of 93.5% and a purity of 97.65%.

[0173] 3) Take the tetrabromophenol tetraiodothiolate lithium salt 103.8 g prepared in the previous step, add 300 mL of water, add 10.6 mL of propionic acid, stir, control the temperature at 55°C for 4 hours; after the reaction is completed, recrystallize in the reaction solution, cool to room temperature, filter, collect the filter cake, dry, and prepare 98.0 grams of pure tetrabromophenol tetraiodothiolate, with a yield of 94.9%, a total yield of 83.5%, and a purity of 99.34%.

[0174] Example 11: Preparation of tetrabromophenol tetraiodothiolate

[0175] 1) Weigh 3,4,5,6-tetraiodophenol thiolate 85.8 g, add acetic acid 400 mL, heat and stir to uniformity at 55°C; add pure water 400 mL, cool to room temperature; add 32 mL (35%) hydrogen peroxide, stir evenly; then slowly drop in 41 g of liquid bromine, stir, control the temperature at 55°C for 5h; after the reaction is completed, cool the reaction solution to room temperature, filter, collect the filter cake, dry, and prepare 110.5 g of tetrabromophenol tetraiodothiolate crude product, with a yield of 94.2% and a purity of 93.29%.

[0176] 2) The crude tetrabromophenol tetrailodophthalein 111.0 g prepared in the previous step was added into acetonitrile 400 mL, and then 10.5 g of potassium bicarbonate was added, and stirred, and reacted at 45 °C for 5 hours. After the reaction was completed, the reaction solution was crystallized, cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrailodophthalein potassium salt 107.5 g, with a yield of 93.8% and a purity of 97.3%.

[0177] 3) The tetrabromophenol tetrailodophthalein potassium salt 107.5 g prepared in the previous step was added into 300 mL of water, and then 10.6 mL of acetic acid was added, and stirred, and reacted at 55 °C for 4 hours. After the reaction was completed, the reaction solution was recrystallized, cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrailodophthalein 98.7 g, with a yield of 94.8% and a purity of 99.23%.

[0178] Example 12: Preparation of tetrabromophenol tetrailodophthalein

[0179] 1) 3,4,5,6-tetraiodophenol sulfonephthalein 85.8 g was weighed, and added into acetic acid 400 mL, and heated and stirred at 45 °C until homogeneous; 400 mL of pure water was added, and cooled to room temperature; 30 mL (35%) of hydrogen peroxide was added, and stirred uniformly; and then 38 g of liquid bromine was slowly added dropwise, and stirred, and reacted at 55 °C for 5 hours. After the reaction was completed, the reaction solution was cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrailodophthalein crude product 111.0 g, with a yield of 94.6% and a purity of 93.2%.

[0180] 2) The tetrabromophenol tetrailodophthalein crude product 111.0 g prepared in the previous step was added into acetonitrile 400 mL, and then 10.5 g of potassium bicarbonate was added, and stirred, and reacted at 45 °C for 5 hours. After the reaction was completed, the reaction solution was crystallized, cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrailodophthalein potassium salt 107.5 g, with a yield of 93.8% and a purity of 97.3%.

[0181] 3) The tetrabromophenol tetrailodophthalein potassium salt 107.5 g prepared in the previous step was added into 300 mL of water, and then 10.6 mL of acetic acid was added, and stirred, and reacted at 55 °C for 4 hours. After the reaction was completed, the reaction solution was recrystallized, cooled to room temperature, filtered, the filter cake was collected and dried to obtain tetrabromophenol tetrailodophthalein 98.7 g, with a yield of 94.8% and a purity of 99.23%.

[0182] The above examples only describe the preferred embodiments of the present application, and do not limit the scope of the present application. Without departing from the design spirit of the present application, various modifications and improvements to the technical solutions of the present application made by those skilled in the art shall fall within the protection scope determined by the claims of the present application.

Claims

1. A process for the preparation of a tetrabromophenol tetrahalosulfonophthalein, characterized in that, The preparation method is as follows: 3,4,5,6-tetrahalophenol sulfonaphthol is used as raw material, and is subjected to bromination by organic carboxylic acid in aqueous solution and liquid bromine oxidized by hydrogen peroxide to obtain tetra-bromophenol tetrahalosulfonaphthol crude product; then salt formation with alkali metal salt in a solvent, crystallization, to obtain tetra-bromophenol tetrahalosulfonaphthol alkali metal salt; and then acid conversion with organic carboxylic acid in aqueous solution, recrystallization, to obtain tetra-bromophenol tetrahalosulfonaphthol pure product; the reaction formula is as follows: ； In the formula, X is Cl, Br or I; M is Li, Na or K; The 3,4,5,6-tetrahalophenol sulfonaphthol is 3,4,5,6-tetrachlorophenol sulfonaphthol, 3,4,5,6-tetrabromophenol sulfonaphthol or 3,4,5,6-tetraiodophenol sulfonaphthol; The organic carboxylic acid is one of formic acid, acetic acid or propionic acid; The alkali metal salt is one of carbonate, bicarbonate or acetate; The solvent is an aprotic solvent; The tetra-bromophenol tetrahalosulfonaphthol alkali metal salt is tetra-bromophenol tetrachlorosulfonaphthol alkali metal salt, tetra-bromophenol tetrabromosulfonaphthol alkali metal salt or tetra-bromophenol tetraiodosulfonaphthol alkali metal salt; The tetra-bromophenol tetrachlorosulfonaphthol alkali metal salt is tetra-bromophenol tetrachlorosulfonaphthol lithium salt, tetra-bromophenol tetrachlorosulfonaphthol sodium salt or tetra-bromophenol tetrachlorosulfonaphthol potassium salt; the tetra-bromophenol tetrabromosulfonaphthol alkali metal salt is tetra-bromophenol tetrabromosulfonaphthol lithium salt, tetra-bromophenol tetrabromosulfonaphthol sodium salt, tetra-bromophenol tetrabromosulfonaphthol potassium salt; the tetra-bromophenol tetraiodosulfonaphthol alkali metal salt is tetra-bromophenol tetraiodosulfonaphthol lithium salt, tetra-bromophenol tetraiodosulfonaphthol sodium salt, tetra-bromophenol tetraiodosulfonaphthol potassium salt; The tetra-bromophenol tetrahalosulfonaphthol is tetra-bromophenol tetrachlorosulfonaphthol, tetra-bromophenol tetrabromosulfonaphthol or tetra-bromophenol tetraiodosulfonaphthol.

2. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 1, characterized by: The preparation method comprises the following specific steps: Oxidation bromination: 3,4,5,6-tetrahalophenol sulfonaphthol (compound a) is added with a certain mass-volume ratio of organic carboxylic acid, heated and stirred uniformly, added with a certain mass-volume ratio of water, cooled to room temperature, added with a certain molar ratio of hydrogen peroxide, stirred uniformly, added with a certain molar ratio of liquid bromine, stirred, and controlled temperature reaction; after the reaction is completed, the reaction liquid is cooled to room temperature, filtered, the filtrate is recovered and reused, the filter cake is collected and dried, to obtain tetra-bromophenol tetrahalosulfonaphthol crude product (compound b); Salt formation purification: the tetra-bromophenol tetrahalosulfonaphthol crude product is added with a certain mass-volume ratio of aprotic solvent and a certain molar ratio of alkali metal salt, stirred, and controlled temperature reaction; after the reaction is completed, crystallization is carried out in the reaction liquid, cooled to room temperature, filtered, the filter cake is collected and dried, to obtain tetra-bromophenol tetrahalosulfonaphthol salt (compound c); Acid conversion purification: the tetra-bromophenol tetrahalosulfonaphthol salt is added with a certain mass-volume ratio of water and a certain molar ratio of organic carboxylic acid, stirred, and controlled temperature reaction; after the reaction is completed, recrystallization is carried out in the reaction liquid, cooled to room temperature, filtered, the filter cake is collected and dried, to obtain tetra-bromophenol tetrahalosulfonaphthol pure product (compound b); The 3,4,5,6-tetrahalophenol sulfonaphthol is 3,4,5,6-tetrachlorophenol sulfonaphthol, 3,4,5,6-tetrabromophenol sulfonaphthol or 3,4,5,6-tetraiodophenol sulfonaphthol; The organic carboxylic acid is one of formic acid, acetic acid or propionic acid; The alkali metal salt is one of carbonate, bicarbonate or acetate; The aprotic solvent is any one or a combination of two of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether; The alkali metal salt of the tetrabromophenol tetrahalosulfone is a tetrabromophenol tetrachlorosulfone alkali metal salt, a tetrabromophenol tetrabromosulfone alkali metal salt, or a tetrabromophenol tetraiodosulfone alkali metal salt; The tetrabromophenol tetrachlorosulfone alkali metal salt is a tetrabromophenol tetrachlorosulfone lithium salt, a tetrabromophenol tetrachlorosulfone sodium salt, or a tetrabromophenol tetrachlorosulfone potassium salt; the tetrabromophenol tetrabromosulfone salt is a tetrabromophenol tetrabromosulfone lithium salt, a tetrabromophenol tetrabromosulfone sodium salt, or a tetrabromophenol tetrabromosulfone potassium salt; the tetrabromophenol tetraiodosulfone salt is a tetrabromophenol tetraiodosulfone lithium salt, a tetrabromophenol tetraiodosulfone sodium salt, or a tetrabromophenol tetraiodosulfone potassium salt; The tetrabromophenol tetrahalosulfone is a tetrabromophenol tetrachlorosulfone, a tetrabromophenol tetrabromosulfone, or a tetrabromophenol tetraiodosulfone.

3. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 2, characterized by: In the oxidation and bromination step: the mass-volume ratio of the 3,4,5,6-tetrahalophenol sulfone to the added organic carboxylic acid is 1:1 to 1:12; the organic carboxylic acid is one of formic acid, acetic acid, or propionic acid; the mass-volume ratio of the 3,4,5,6-tetrahalophenol sulfone to the added water is 1:1 to 1:12; the molar ratio of the 3,4,5,6-tetrahalophenol sulfone to the added liquid bromine is 1:2 to 1:3; the molar ratio of the hydrogen peroxide to the 3,4,5,6-tetrahalophenol sulfone is 1:1 to 1:6; the molar ratio of the hydrogen peroxide to the liquid bromine is 1:1 to 1:2; the temperature-controlled reaction temperature is 20 to 70°C; and the temperature-controlled reaction time is 1 to 12 hours.

4. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 3, characterized by: The purity of the starting material 3,4,5,6-tetrahalophenol sulfone is 90%, and the yield of the crude tetrabromophenol tetrahalosulfone prepared by oxidation and bromination is 92%, and the purity is 93%.

5. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 2, characterized by: In the salt formation and purification step: the amount of alkali metal salt used is 1.0 to 1.5 eq of tetrabromophenol tetrahalosulfone; the selected alkali metal salt is lithium bicarbonate or sodium bicarbonate or potassium bicarbonate; the mass-volume ratio of the crude tetrabromophenol tetrahalosulfone to the aprotic solvent is 1:2 to 1:12 mL; the aprotic solvent is any one of acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether, benzene, toluene, and xylene; the temperature-controlled reaction is 30 to 70°C; and the reaction time is 1 to 12 hours.

6. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 5, characterized by: Through the salt formation reaction and crystallization using the reaction system itself, the yield of the tetrabromophenol tetrahalosulfone alkali metal salt prepared is 93%, and the purity is 97.0%.

7. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 2, characterized by: In the acid transfer purification step: the molar ratio of the tetrabromophenol tetrahalosulfone salt to the added organic carboxylic acid is 1:1 to 1:6; the organic carboxylic acid is one of formic acid, acetic acid, or propionic acid; the mass-volume ratio of the tetrabromophenol tetrahalosulfone salt to the added water is 1:1 to 1:12 mL; the temperature-controlled reaction temperature is 35 to 90°C; and the temperature-controlled reaction time is 1 to 12 hours.

8. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 7, characterized by: The yield of the pure product of tetrabromophenol tetrabromophthalide is 94% and the purity is 99.0% by using the self-reaction system for recrystallization through the transacid reaction.

9. The method for preparing tetrabromophenol tetrabromophthalide according to claim 3, characterized in that: In the step of oxidative bromination, the mass-volume ratio of 3, 4, 5, 6-tetrahalophenol phthalide to carboxylic acid is 1:2-1:6; the mass-volume ratio of 3, 4, 5, 6-tetrahalophenol phthalide to water is 1g:2-6mL; the molar ratio of 3, 4, 5, 6-tetrabromophenol phthalide to liquid bromine is 1:2-1:3; the molar ratio of hydrogen peroxide to 3, 4, 5, 6-tetrahalophenol phthalide is 1:1-1:6; the molar ratio of hydrogen peroxide to liquid bromine is 1:1-1:2; the temperature of the controlled temperature reaction is 25-60℃; and the time of the controlled temperature reaction is 1-6 hours; In the step of salt formation and purification, the mass-volume ratio of tetrabromophenol tetrabromophthalide to aprotic solvent is 1:2-1:6; the aprotic solvent is one of acetone, acetonitrile, dioxane, ethyl acetate or dichloromethane; the temperature of the controlled temperature reaction is 35-65℃; and the time of the reaction is 1-6 hours; In the step of transacid purification, the molar ratio of tetrabromophenol tetrabromophthalide salt to organic carboxylic acid is 1:2-1:4; the mass-volume ratio of tetrabromophenol tetrabromophthalide salt to water is 1:2-1:6; the temperature of the controlled temperature reaction is 40-70℃; and the time of the controlled temperature reaction is 1-6 hours.

10. A process for the preparation of tetrabromophenol tetrahalothio-phthalein according to claim 9, characterized by: The first purification is completed by oxidative bromination, the second purification is completed by crystallization using aprotic solvent for salt formation, and the third purification is completed by recrystallization using carboxylic acid aqueous solution for transacid, so that the total yield of the product of tetrabromophenol tetrabromophthalide alkali metal salt is more than 80% and the purity is more than 99.0%.

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