CN116425714A - Preparation method of tetrabromophenol tetrahalogen sulfophthalein - Google Patents

Abstract

The invention relates to the technical field of chemical medicine preparation, in particular to a preparation method of tetrabromophenol tetrahalosulfophthalein, which takes 3,4,5, 6-tetrahalophenol sulfophthalein as a raw material, and liquid bromine is oxidized and brominated by hydrogen peroxide in aqueous solution to prepare a tetrabromophenol tetrahalosulfophthalein crude product, and then the tetrabromophenol tetrahalosulfophthalein crude product and alkali salt are salified in aprotic solvent, and crystallized to prepare the tetrabromophenol tetrahalosulfophthalein salt; then, the tetrabromophenol tetrahalosulfophthalein is subjected to acid conversion and recrystallization in an aqueous solution with organic carboxylic acid to obtain a tetrabromophenol tetrahalosulfophthalein pure product; the invention provides a preparation method of tetrabromophenol tetrahalogen sulfophthalein, which has the advantages of low cost, high yield and high purity, and the method is simple, mild in condition, high in yield and high in purity, and is beneficial to mass production.

Description

Preparation method of tetrabromophenol tetrahalogen sulfophthalein

Technical Field

The invention relates to the technical field of chemical medicine preparation, in particular to a preparation method of tetrabromophenol tetrahalogen sulfophthalein.

Background

Tetrabromophenol tetrahalosulfophthalein (Tetrabromo phenol tetrahalogenated suofonephthalein, TBPTHSP) belongs to sulfophthalein compounds, has high stability and good fixation effect, and is an important dye, and the structural formula is as follows:

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

The traditional synthesis method of tetrabromophenol tetrahalosulfophthalein takes tetrahalophenol sulfophthalein (phenol tetrahalosulfophthalein) as a raw material and is prepared by bromination reaction in glacial acetic acid. The method uses a large amount of liquid bromine, a large amount of hydrogen bromide generated in the reaction process needs to be neutralized and treated, reagents are wasted, the reaction is incomplete, the impurities are high, the purification is difficult, the yield is low, the purity is low, and the mass production is difficult.

Therefore, how to develop a preparation method of tetrabromophenol tetrahalogen sulfophthalein with high yield, high purity and low cost, which is beneficial to industrial production, is a technical problem to be solved at present.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide the preparation method of tetrabromophenol tetrahalogen sulfophthalein, which has the advantages of simple operation, high yield, high purity and low cost and is beneficial to industrial production.

In order to achieve the above purpose, the present invention provides the following technical solutions:

the preparation method is that 3,4,5, 6-tetrahalophenol sulfophthalein is taken as raw material, and the raw material is mixed with organic carboxylic acid in aqueous solution, and liquid bromine is oxidized and brominated by hydrogen peroxide to prepare crude tetrabromophenol tetrahalophthalein; then salifying with alkali metal salt in solvent, crystallizing to obtain tetrabromophenol tetrahalogen sulfophthalein alkali metal salt; then, the tetrabromophenol tetrahalosulfophthalein is subjected to acid conversion and recrystallization in an aqueous solution with organic carboxylic acid to obtain a tetrabromophenol tetrahalosulfophthalein pure product; the reaction formula is as follows:

In the formula (2), X is Cl, br or I; m is Li, na or K;

the 3,4,5, 6-tetrahalophenol sulfophthalein is 3,4,5, 6-tetrachlorophenol sulfophthalein, 3,4,5, 6-tetrabromophenol sulfophthalein or 3,4,5, 6-tetraiodophenol sulfophthalein;

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 tetrabromophenol tetrahalosulfophthalein alkali metal salt is tetrabromophenol tetrachlorosulfophthalein alkali metal salt, tetrabromophenol tetrabromosulfophthalein alkali metal salt or tetrabromophenol tetraiodosulfophthalein alkali metal salt;

the tetrabromophenol tetrachloro-sulfonephthalein salt is tetrabromophenol tetrachloro-sulfonephthalein lithium salt, tetrabromophenol tetrachloro-sulfonephthalein sodium salt or tetrabromophenol tetrachloro-sulfonephthalein potassium salt; the tetrabromophenol tetrabromosulfonephthalein salt is tetrabromophenol tetrabromosulfonephthalein lithium salt, tetrabromophenol tetrabromosulfoephthalein sodium salt and tetrabromophenol tetrabromosulfoephthalein potassium salt; the tetrabromophenol tetraiodosulfonephthalein salt is tetrabromophenol tetraiodosulfonephthalein lithium salt, tetrabromophenol tetraiodosulfonephthalein sodium salt and tetrabromophenol tetraiodosulfonephthalein potassium salt;

the tetrabromophenol tetrahalosulfophthalein is tetrabromophenol tetrachlorosulfophthalein, tetrabromophenol tetrabromosulfophthalein or tetrabromophenol tetraiodosulfophthalein.

A preparation method of tetrabromophenol tetrahalogen sulfophthalein comprises the following specific steps:

1) Oxidizing and brominating: adding organic carboxylic acid with a certain mass-volume ratio into 3,4,5, 6-tetrahalophenol sulfophthalein (compound a), heating and stirring uniformly, adding water with a certain mass-volume ratio, cooling to room temperature, adding hydrogen peroxide with a certain mole ratio, stirring uniformly, adding liquid bromine with a certain mole ratio, stirring, and performing temperature control reaction; after the reaction is finished, cooling the reaction liquid to room temperature, filtering, recycling and applying the filtrate, collecting a filter cake, and drying to obtain a tetrabromophenol tetrahalogen sulfophthalein crude product (a compound b);

2) Salt formation and purification: adding an aprotic solvent with a certain mass-volume ratio into the tetrabromophenol tetrahalogen sulfophthalein crude product, adding alkali metal salt with a certain molar ratio, stirring, and performing temperature control reaction; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain tetrabromophenol tetrahalogen sulfophthalein salt (a compound c);

3) Acid conversion and purification: adding water with a certain mass volume ratio into tetrabromophenol tetrahalogen sulfophthalein salt, adding organic carboxylic acid with a certain molar ratio, stirring, and performing temperature control reaction; after the reaction is finished, recrystallizing in a reaction solution, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a pure tetrabromophenol tetrahalosulfophthalein (compound b);

The 3,4,5, 6-tetrahalophenol sulfophthalein is 3,4,5, 6-tetrachlorophenol sulfophthalein, 3,4,5, 6-tetrabromophenol sulfophthalein or 3,4,5, 6-tetraiodophenol sulfophthalein;

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 can be any one or two 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;

the tetrabromophenol tetrahalosulfophthalein salt is tetrabromophenol tetrachlorosulfophthalein alkali metal salt, tetrabromophenol tetrabromosulfophthalein alkali metal salt or tetrabromophenol tetraiodosulfophthalein alkali metal salt;

the tetrabromophenol tetrachloro-sulfonephthalein salt is tetrabromophenol tetrachloro-sulfonephthalein lithium salt, tetrabromophenol tetrachloro-sulfonephthalein sodium salt or tetrabromophenol tetrachloro-sulfonephthalein potassium salt; the tetrabromophenol tetrabromosulfonephthalein salt is tetrabromophenol tetrabromosulfonephthalein lithium salt, tetrabromophenol tetrabromosulfoephthalein sodium salt and tetrabromophenol tetrabromosulfoephthalein potassium salt; the tetrabromophenol tetraiodosulfonephthalein salt is tetrabromophenol tetraiodosulfonephthalein lithium salt, tetrabromophenol tetraiodosulfonephthalein sodium salt and tetrabromophenol tetraiodosulfonephthalein potassium salt;

The tetrabromophenol tetrahalosulfophthalein is tetrabromophenol tetrachlorosulfophthalein, tetrabromophenol tetrabromosulfophthalein or tetrabromophenol tetraiodosulfophthalein.

The experimental results of the oxidizing bromination step show that:

when the acid selected by the invention is organic carboxylic acid, the effect of dissolving the phenolsulfonephthalein is good, and when other acids are selected, the solubility of the phenolsulfonephthalein is low, so that the reaction effect is affected;

the addition proportion of the selected organic carboxylic acid is too low, the acidification is insufficient, the addition proportion is too high, and the reagent is wasted; the volume of water is preferably equal to the volume of acid;

the bromination reaction is carried out, the selected liquid bromine is more than 2 times equivalent of the phenolsulfonephthalein and can be fully completed, which is far lower than at least 4 times equivalent in the prior art, thus saving a large amount of liquid bromine;

the hydrogen peroxide used in the oxidation reaction is at least more than 2 times equivalent of the phenolsulfonephthalein, namely more than 1 time equivalent of liquid bromine, so that the oxidation can be fully performed;

the temperature-controlled reaction temperature is lower than 25 ℃, the reaction is too slow, the reaction temperature is higher than 70 ℃, side reactions are easy to cause, and the yield and purity are affected.

Further, the invention provides a preparation method of tetrabromophenol tetrahalogen sulfophthalein, and the preparation method comprises the following steps of: the mass volume ratio of the 3,4,5, 6-tetrahalophenol sulfophthalein to the added organic carboxylic acid is 1 g:1-12 mL; 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 sulfophthalein to the added water is 1:1-1:12; the molar ratio of the 3,4,5, 6-tetrabromophenol sulfophthalein to the added liquid bromine is 1:2-1:3; the molar ratio of the hydrogen peroxide to the 3,4,5, 6-tetrahalophenol sulfophthalein is 1:1-1:6; the molar ratio of the hydrogen peroxide to the liquid bromine is 1:1-1:2; the temperature of the temperature-controlled reaction is 20-70 ℃; the temperature control reaction time is 1-12 hours;

In the oxidizing bromination step, the bromine amount of liquid used for bromination is saved by more than 50 percent compared with the prior art; the purity of the reaction initial raw material 3,4,5, 6-tetrahalophenol sulfophthalein is 90%, the yield of the tetrabromophenol tetrahalophthalein crude product prepared by oxidizing and brominating is 92%, and the purity is 93%;

the experimental results of the salification purification step show that:

when the alkali salt selected by the invention is carbonate, the reaction system is too dark due to stronger alkalinity; when the alkali is acetate, the reaction time is too long and the reaction is not complete due to the weak alkali; when the alkali is bicarbonate, the alkali is moderate, the reaction is very fast and complete; if the amount of the alkali is too small, namely less than 1eq, the reaction is incomplete, and the yield is affected; if the amount of the alkali is too large, namely more than 1.5eq, alkali residues exist, the alkali is not easy to remove, and the purity is affected; the alkali amount is selected to be in the range of 1-1.5 eq, and the reaction effect is relatively good;

when the solvent selected in the salification reaction is a proton solvent, the solvent can not completely react, and the color reaction of tetrabromophenol tetrahalosulfophthalein can be caused, so that the product is too deep; when aprotic solvents are selected, the reaction can be completed, 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;

Compared with the crude tetrabromophenol tetrahalogen sulfophthalein, the aprotic solvent has the advantages of over small volume, insufficient reaction and lower purity; when the volume of the aprotic solvent is too large compared with that of the tetrabromophenol tetrahalogen sulfophthalein crude product, the yield is low; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein crude product to the aprotic solvent is 1:1-1:12, the yield is higher, the purity is higher, and the effect is better;

when the reaction temperature is lower than 30 ℃, the reaction rate is too slow, the reaction time is too long, and the reaction efficiency is low; when the reaction temperature is higher than 70 ℃, side reactions are easy to be initiated, and the color of the product is deepened;

the reaction time is less than 2 hours, the reaction is incomplete, the yield is low, the purity is low, and the free impurities are high; the reaction time is longer than 10 hours, the reaction time is too long, the side reaction is more, the impurity is high, and the purity is low;

after the salification reaction, the tetrabromophenol tetrahalogen sulfophthalein alkali metal salt mainly contains three substances: the first class is a macromolecule after salification, namely tetrabromophenol tetrahalogen sulfophthalein salt, the second class is a small molecule incapable of salifying, and the third class is a small molecule capable of salifying; in the salt forming reaction, a salt forming solvent is used for realizing primary crystallization, small molecules which form salt and small molecules which do not form salt are both dissolved in crystallization mother liquor, while tetrabromophenol tetrahalogen sulfophthalein salt is indissolvable in the crystallization solvent, so that separation of products and impurities is realized, and the purification effect is achieved.

Further, the invention provides a preparation method of tetrabromophenol tetrahalogen sulfophthalein, and the preparation method comprises the following steps of: the dosage of the alkali metal salt is 1.0-1.5 eq of tetrabromophenol tetrahalogen sulfophthalein; the alkali metal salt selected is bicarbonate, preferably lithium bicarbonate, sodium bicarbonate or potassium bicarbonate; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein crude product 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 control reaction is 30-70 ℃; the reaction time is 1-12 hours;

in the salification and purification step, the self reaction system is used for crystallization through salification reaction, and the yield of the prepared tetrabromophenol tetrahalogen sulfophthalein alkali metal salt is 93 percent, and the purity is 97.0 percent;

the experimental results in the acid conversion purification step show that:

when the acid selected by acid conversion is other acid, the stability of the product is affected, and the purity is reduced; the organic carboxylic acid is selected from one of formic acid, acetic acid or propionic acid, and when other organic carboxylic acids are selected, the purity is lower after recrystallization; when the addition amount of the organic carboxylic acid is 1 equivalent, acidification is insufficient, the yield is lower and is higher than 3 equivalents, the yield is reduced, and when the molar ratio of tetrabromophenol tetrahalogen sulfophthalein salt to the added organic carboxylic acid is 1:1-1:3, the yield is higher, the purity is higher, and the effect is better;

The purification in the acid conversion purification process is realized by recrystallization in an organic acid aqueous solution; in the recrystallization process, a small amount of macromolecular impurities are dissolved in an organic acid aqueous solution, and tetrabromophenol tetrahalosulfophthalein is difficult to dissolve in the organic acid aqueous solution, so that the tetrabromophenol tetrahalosulfophthalein is purified again;

in the acid conversion purification process, the water volume is too small, stirring and acidification are insufficient, the yield is reduced, the purity is reduced, the volume of water is too large, the product is dissolved in the solution again, the yield is affected, the mass-volume ratio of tetrabromophenol tetrahalogen sulfophthalein salt to added water is 1:2-1:10, the yield is higher, the purity is higher, and the effect is better; the temperature-controlled reaction temperature is lower than 35 ℃, the acidification reaction time is too long, the recrystallization effect is reduced, the yield is lower, the purity is higher than 75 ℃, the yield is reduced, and the temperature-controlled reaction temperature is 35-70 ℃; the temperature control reaction time is 1-10 hours, the yield is higher, the purity is higher, and the effect is better;

further, the invention provides a preparation method of tetrabromophenol tetrahalogen sulfophthalein, which comprises the following steps of: the molar ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added organic carboxylic acid is 1:1-1:6; the organic carboxylic acid is one of formic acid, acetic acid or propionic acid; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added water is 1:1-1:12; the temperature control reaction temperature is 35-90 ℃; the reaction time of temperature control is 1 to 12 hours;

In the acid conversion purification step, the tetrabromophenol tetrahalogen sulfophthalein is recrystallized by using a self-reaction system through acid conversion reaction, so that the yield of the prepared tetrabromophenol tetrahalogen sulfophthalein is 94%, and the purity is 99.0%;

further, in the preparation method of tetrabromophenol tetrahalogen sulfophthalein, in the oxidizing bromination step, the mass volume ratio of the 3,4,5, 6-tetrahalogen phenol sulfophthalein to the added carboxylic acid is 1:2-1:6; the mass volume ratio of the 3,4,5, 6-tetrahalophenol sulfophthalein to the added water is 1:2-1:6; the molar ratio of the 3,4,5, 6-tetrabromophenol sulfophthalein to the added liquid bromine is 1:2-1:3; the molar ratio of the hydrogen peroxide to the 3,4,5, 6-tetrahalophenol sulfophthalein is 1:1-1:6; the molar ratio of the hydrogen peroxide to the liquid bromine is 1:1-1:2; the temperature of the temperature-controlled reaction is 25-60 ℃; the temperature control reaction time is 1-6 hours;

in the salifying purification step, the mass volume ratio of the crude tetrabromophenol tetrahalogen sulfophthalein to the aprotic solvent is 1:2-1:6; the aprotic solvent is one of acetone, acetonitrile, dioxane, ethyl acetate or dichloromethane; the temperature control reaction is carried out at 35-65 ℃; the reaction time is 1-6 hours;

In the acid conversion purification step, the molar ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added organic carboxylic acid is 1:2-1:4; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added water is 1:2-1:6; the temperature of the temperature-controlled reaction is 40-70 ℃; the reaction time of temperature control is 1 to 6 hours;

the method comprises the steps of oxidizing and brominating to finish the first purification, crystallizing by using an aprotic solvent for salifying to finish the second purification, recrystallizing by using a carboxylic acid aqueous solution for transferring acid to finish the third purification, and finally obtaining tetrabromophenol tetrahalosulfophthalein alkali metal salt product with the purity of more than 80% and the purity of more than 99.0%;

furthermore, the invention provides a preparation method of tetrabromophenol tetrahalogen sulfophthalein, which improves the reaction efficiency through oxidation bromination, greatly reduces the consumption of liquid bromine, reduces the cost and improves the yield; the purity of tetrabromophenol tetrahalogen sulfophthalein salt is improved through salification and purification; the purity of tetrabromophenol tetrahalosulfophthalein is further improved by acid conversion purification, and the total yield is improved.

Compared with the prior art, the preparation method of tetrabromophenol tetrahalogen sulfophthalein has the following beneficial effects:

The preparation method of tetrabromophenol tetrahalogen sulfophthalein has high yield, high purity and low cost, is simple, has mild conditions, is beneficial to mass production, and is suitable for large-scale popularization and application.

Detailed Description

The technical scheme of the present invention will be clearly and completely described in the following detailed description. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Example 1: comparison of implementation Effect in oxidative bromination Process

(1) Selection of acids

70.0 g (0.1 moL, purity 90.12%, the same applies below) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 5 parts are respectively weighed, formic acid, acetic acid, propionic acid, butyric acid and hydrochloric acid are respectively added according to the mass volume ratio of 1:3, and the mixture is heated and stirred at 60 ℃ until being uniform; adding water with the mass to volume ratio, and cooling to room temperature; adding 2.2eq of hydrogen peroxide, and uniformly stirring; 2.2eq equivalent of liquid bromine is added, stirred and reacted for 2 hours at the temperature of 40 ℃; after the reaction is finished, the reaction liquid is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare a tetrabromophenol tetrabromosulfonephthalein crude product, and relevant experimental data are shown in a table I:

TABLE I

The data in Table I indicate that: the yield and purity of three organic carboxylic acids of formic acid, acetic acid or propionic acid are obviously higher than those of butyric acid or hydrochloric acid; it can be seen that three organic carboxylic acids, formic acid, acetic acid or propionic acid, perform well.

(2) Selection of acid feed ratio

70.0 g (0.1 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 5 parts are respectively weighed, acetic acid is respectively added according to the mass-volume ratio of 1:1, 1:2, 1:3, 1:6 and 1:7, and the mixture is heated and stirred at 50 ℃ until the mixture is uniform; adding water according to the mass-volume ratio of 1:3, and cooling to room temperature; adding 2.2eq of hydrogen peroxide, and uniformly stirring; 2.2eq equivalent of liquid bromine is added, stirred and reacted for 2 hours at the temperature of 40 ℃; after the reaction is finished, the reaction liquid is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare a tetrabromophenol tetrabromosulfonephthalein crude product, and relevant experimental data are shown in a table II:

table II

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

(3) Selection of the Water addition ratio

70.0 g (0.1 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 5 parts are respectively weighed, acetic acid is respectively added according to the mass-volume ratio of 1:2, and the mixture is heated and stirred at 50 ℃ until the mixture is uniform; adding water with the same mass volume ratio, adding acetic acid according to the mass volume ratio of 1:1, 1:2, 1:3, 1:6 and 1:7 respectively, and cooling to room temperature; adding 2.2eq of hydrogen peroxide, and uniformly stirring; 2.2eq equivalent of liquid bromine is added, stirred and reacted for 2 hours at the temperature of 40 ℃; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare a tetrabromophenol tetrabromosulfonephthalein crude product, and relevant experimental data are shown in a table III:

Table III

The data in Table III indicate that: the water adding ratio is lower than 1:1 or higher than 1:6, the yield is reduced, and the purity is reduced; when the water adding ratio is 1:2 to 1:6, the yield is higher, the purity is higher, and the implementation effect is better.

(4) Selection of liquid bromine feed equivalent

70.0 g (0.1 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 5 parts of the 3,4,5, 6-tetrabromophenol sulfophthalein are respectively weighed, acetic acid is added according to the mass-volume ratio of 1:2, and the mixture is heated and stirred at 50 ℃ until the mixture is uniform; adding water according to the mass-volume ratio of 1:2, and cooling to room temperature; adding 3.2eq of hydrogen peroxide, and uniformly stirring; adding liquid bromine with equivalent weight of 1.5, 2.0, 2.5, 3.0 and 3.5eq, stirring, and reacting for 2 hours at the temperature of 40 ℃; after the reaction is finished, the reaction liquid is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare a tetrabromophenol tetrabromosulfonephthalein crude product, and relevant experimental data are shown in a table IV:

table IV

The data in Table IV indicate that: the liquid bromine is fed with too little 1.5 equivalent, the yield is low, and the purity is low; the liquid bromine feeding amount is more than 2.0 equivalents, the purity and the yield are obviously increased compared with 1.5 equivalents, but the yield and the purity are not obviously increased compared with 2.0 equivalents; the liquid bromine is fed at 3.5 equivalents, the yield is not increased, and the purity begins to be reduced; the implementation effect of the bromine addition of the visible liquid is better between 2.0 and 3.0 equivalents;

(5) Selection of hydrogen peroxide feeding equivalent

70.0 g (0.1 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 5 parts of the 3,4,5, 6-tetrabromophenol sulfophthalein are respectively weighed, acetic acid is added according to the mass-volume ratio of 1:2, and the mixture is heated and stirred at 50 ℃ until the mixture is uniform; adding water according to the mass-volume ratio of 1:2, and cooling to room temperature; adding 1.5, 2.0, 4.0, 6.0 and 6.5eq hydrogen peroxide, and uniformly stirring; adding 2.0eq of liquid bromine, stirring, and controlling the temperature to be 40 ℃ for reaction for 2 hours; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare a tetrabromophenol tetrabromosulfonephthalein crude product, and relevant experimental data are shown in Table V:

table V

The data in Table V indicate that: the hydrogen peroxide is added with too small amount of 1.5 equivalents, so that the bromine in the hydrogen bromide generating solution can not be completely oxidized to participate in the bromination reaction, and the yield and the purity are low; the hydrogen peroxide feeding amount is more than 2.0 equivalents, the purity and the yield are obviously increased compared with 1.5 equivalents, the hydrogen peroxide feeding amount reaches 6.0 equivalents, and the yield and the purity are not obviously increased compared with 2.0 equivalents; the liquid bromine is added into the reactor at 6.5 equivalents, the yield is slightly reduced, and the purity is slightly reduced; the implementation effect is better when the hydrogen peroxide is added between 2.0 and 6.0 equivalents;

(6) Selection of reaction temperature and time

70.0 g (0.1 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 5 parts of the 3,4,5, 6-tetrabromophenol sulfophthalein are respectively weighed, acetic acid is added according to the mass-volume ratio of 1:2, and the mixture is heated and stirred at 50 ℃ until the mixture is uniform; adding water according to the mass-volume ratio of 1:2, and cooling to room temperature; adding 2.5eq hydrogen peroxide, and stirring uniformly; adding 2.0 equivalents of liquid bromine, stirring, controlling the temperature to be 20 ℃, 25 ℃, 40 ℃, 60 ℃ and 65 ℃ for reaction for 1-6 hours, detecting the reaction, cooling the reaction liquid to room temperature after the reaction is finished, filtering, collecting a filter cake, and drying to obtain a tetrabromophenol tetrabromosulfophthalein crude product, wherein relevant experimental data are shown in table VI:

Table VI

The data in Table VI indicate that: the reaction temperature is 20 ℃, the reaction time is 6 hours, the yield is low, the purity is low, and the reaction time is too long; the reaction temperature is 60 ℃, the reaction time is 1 hour, the reaction is too severe although the reaction time is short, the byproducts are more, and the yield and the purity are reduced; the reaction temperature is 25-60 ℃, the reaction time is 1-6 hours, the reaction yield is high, the purity is high, and the implementation effect is good;

example 2: comparison of implementation effects in salt formation purification

1) 2100 g (3.0 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, acetic acid 4200mL is added according to the mass volume ratio of 1:2, heating and stirring are carried out at 60 ℃ until the mixture is uniform, 4200mL of water is added, cooling is carried out to room temperature, 7.5moL of hydrogen peroxide is added, stirring is carried out uniformly, 959 g of liquid bromine (6.0 moL) is added, stirring is carried out, and the temperature is controlled to 45 ℃ for reaction for 2 hours; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare 2800 g of tetrabromophenol tetrabromo sulfophthalein crude product, the yield is 94.7%, the purity is 93.15%, and the product is used for the following experiments;

(1) Selection of alkali salts

Weighing 5 parts of tetrabromophenol tetrabromosulfonephthalein crude product obtained in the last step, adding acetonitrile into 98.6 g (0.1 moL) of each part according to a mass-volume ratio of 1:4, adding 1.1ep lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, sodium carbonate and sodium acetate into each part, stirring, and controlling the temperature to be 50 ℃ for reaction for 4 hours; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a corresponding salt of tetrabromophenol tetrabromosulfonephthalein, wherein relevant experimental data are shown in a table VII:

Table VII

The data in Table VII shows that: the alkali salt is sodium carbonate, the alkalinity is too strong, the side reaction is increased, the yield is low, the purity is low, the alkali salt is sodium acetate, the alkalinity is too weak, the reaction is slow, the yield is low, and the purity is low; the alkali salt is selected from lithium bicarbonate, sodium bicarbonate and potassium bicarbonate, so that the yield is high, the purity is high, and the implementation effect is good;

(2) Selection of base salt feed equivalent

Weighing 5 parts of tetrabromophenol tetrabromosulfonephthalein crude product obtained in the last step, adding acetonitrile into 98.6 g (0.1 moL) of each part according to a mass-volume ratio of 1:4, adding sodium bicarbonate of 0.9, 1.0, 1.1, 1.5 and 1.6ep respectively, stirring, and controlling the temperature to be 50 ℃ for reaction for 4 hours; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain tetrabromophenol tetrabromo sulfophthalein sodium salt, wherein relevant experimental data are shown in a table VIII:

table VIII

The data in Table VIII show that: the alkali salt is added in an amount of 0.9 equivalent, the amount of the alkali salt is too small, the reaction yield is low, and the purity is slightly low; the amount of the alkali salt is 1.6 equivalent, the side reaction is increased, the yield is low, and the purity is low; 1 to 1.5 equivalents of alkali salt is added, the yield is high, the purity is high, and the implementation effect is good;

(3) Selection of salt-forming solvents

Weighing 6 parts of tetrabromophenol tetrabromosulfonephthalein crude product obtained in the last step, adding acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane and any other solvent according to a mass-volume ratio of 1:4 into each part of 98.6 g (0.1 moL), respectively adding 1.1ep sodium bicarbonate, stirring, and controlling the temperature to be 50 ℃ for reaction for 4 hours; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain tetrabromophenol tetrabromo sulfophthalein sodium salt, wherein relevant experimental data are shown in Table IX:

Table IX

The data in Table IX indicate that: any other solvent is selected as the salifying solvent, so that the yield is lower and the purity is lower; the acetone, acetonitrile, dioxane, ethyl acetate and methylene dichloride are selected, so that the yield is high, the purity is high, and the implementation effect is good;

(4) Selection of the feed ratio of the salifying solvent

Weighing 5 parts of tetrabromophenol tetrabromosulfonephthalein crude product obtained in the last step, wherein each part is 98.6 g (0.1 moL), adding acetonitrile according to the mass-volume ratio of 1:1, 1:2, 1:4, 1:6 and 1:7, adding 1.1ep sodium bicarbonate respectively, stirring, and controlling the temperature to be 50 ℃ for reaction for 4 hours; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain tetrabromophenol tetrabromo sulfophthalein sodium salt, wherein relevant experimental data are shown in Table X:

table X

The data in Table X indicate that: the mass-volume ratio of the salifying solvent is 1:1, the reaction is insufficient, the yield is low, and the purity is low; when the mass-to-volume ratio is 1:7, the system is overlarge, the yield is lower, and the solvent is wasted; the mass volume ratio is selected to be in the range of 1:2 to 1:6, the yield is high, the purity is high, and the implementation effect is good;

(5) Selection of salt formation reaction temperature and time

Weighing 5 parts of tetrabromophenol tetrabromosulfonephthalein crude product obtained in the last step, wherein each part is 98.6 g (0.1 moL), adding acetonitrile according to a mass-volume ratio of 1:3, adding 1.1ep sodium bicarbonate, stirring, and performing temperature control reaction according to 30, 35, 55, 65 and 70 ℃ respectively; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain tetrabromophenol tetrabromo sulfophthalein sodium salt, wherein relevant experimental data are shown in Table XI:

Table XI

The data in Table XI indicate that: the reaction temperature is 30 ℃, the reaction time is 6 hours, the temperature is too low, the time is too long, the yield is low, and the purity is low; the reaction time is 70 ℃, the reaction time is 1 hour, the temperature is too high, the side reaction is increased, the yield is low, and the purity is low; the reaction temperature is 35 to 65 ℃, the reaction time is 1 to 6 hours, the yield is high, the purity is high, and the implementation effect is good;

example 3: comparison of the effect of the implementation in the purification of the trans-acids

1) 1) weighing 2100 g (3.0 moL) of 3,4,5, 6-tetrabromophenol sulfophthalein, adding 4200mL of acetic acid according to a mass-volume ratio of 1:2, heating and stirring to be uniform, adding 4200mL of water, cooling to room temperature, adding 7.5moL of hydrogen peroxide, stirring to be uniform, adding 959 g of liquid bromine (6.0 moL), stirring, and controlling the temperature to react for 2 hours at 45 ℃; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, and a filter cake is collected and dried to prepare 2782 g of tetrabromophenol tetrabromo sulfophthalein crude product, the yield is 94.1%, the purity is 94.46%, and the product is used for the following experiments;

2) 2782 g (2.823 moL) of tetrabromophenol tetrabromosulfonephthalein crude product prepared in the previous step is added with 8346mL of acetonitrile according to the mass-volume ratio of 1:3, 260.9 g (3.105 moL) of sodium bicarbonate with the concentration of 1.1ep is added, and the mixture is stirred and reacted for 3 hours at the temperature of 55 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 2653 g of tetrabromophenol tetrabromo sulfophthalein sodium salt, wherein the yield is 93.3% and the purity is 97.55%, and the tetrabromophenol tetrabromo sulfophthalein sodium salt is used for the following experiment;

(1) Selection of acids

Weighing 5 parts of tetrabromophenol tetrabromo sulfophthalein sodium salt prepared in the previous step, adding water into 100.7 g (0.1 moL) of each part according to a certain mass-volume ratio of 1:4, adding organic carboxylic acid into the mixture according to 2.0eq, stirring the mixture, and controlling the temperature to be 55 ℃ for reaction for 2 hours; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a pure tetrabromophenol tetrabromosulfonephthalein product, wherein the relevant experimental data are shown in Table XII:

table XII

The data in Table XII show that: the yield and purity of three organic carboxylic acids of formic acid, acetic acid or propionic acid are obviously higher than those of butyric acid or hydrochloric acid; it can be seen that three organic carboxylic acids, formic acid, acetic acid or propionic acid, perform well.

(2) Selection of the charge equivalent of organic carboxylic acid

Weighing 5 parts of tetrabromophenol tetrahalogen sulfophthalein sodium salt prepared in the previous step, adding water into 100.7 g (0.1 moL) of each part according to a certain mass-volume ratio of 1:4, adding acetic acid into the mixture according to a certain mass-volume ratio of 1.5eq, 2.0eq, 3.0eq, 4.0eq and 4.5eq, stirring the mixture, and controlling the temperature to react for 2 hours at 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a pure tetrabromophenol tetrabromosulfonephthalein product, wherein the relevant experimental data are shown in a table XIII:

table XIII

The data in table XIII show that: the acetic acid feeding proportion is 1.0 equivalent, and the yield is too low and the purity is not improved due to insufficient acidification; the acetic acid feeding proportion is 4.5 equivalents, acid dissolution occurs, and the yield is reduced; when the feeding proportion of the acetic acid is 2.0-4.0 equivalents, the yield is higher, the purity is higher, and the implementation effect is better;

(3) Selection of the Water feed ratio

Weighing 5 parts of tetrabromophenol tetrahalogen sulfophthalein sodium salt prepared in the previous step, adding water into each 100.7 g (0.1 moL) of tetrabromophenol tetrahalogen sulfophthalein sodium salt according to a certain mass-volume ratio of 1:1, 1:2, 1:3, 1:6 and 1:7, adding acetic acid into each 1.1eq, stirring, and controlling the temperature to react for 2 hours at 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a pure tetrabromophenol tetrabromosulfonephthalein product, wherein the relevant experimental data are shown in Table XIV:

table XIV

The data in Table XIV show that: the water feeding ratio is 1:1, the acidification is insufficient, the yield is low, and the purity is not improved; the water feeding ratio is 1:7, and the yield is too low; the water feeding ratio is 1:2 to 1:6, the yield is higher, the purity is higher, and the implementation effect is better;

(4) Selection of acidification temperature and time

Weighing 5 parts of tetrabromophenol tetrahalogen sulfophthalein sodium salt prepared in the previous step, adding water into each 100.7 g (0.1 moL) of tetrabromophenol tetrahalogen sulfophthalein sodium salt according to a certain mass-volume ratio of 1:3, adding acetic acid into each 1.1eq, stirring, and performing temperature control reaction; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a pure tetrabromophenol tetrabromosulfonephthalein product, wherein relevant experimental data are shown in Table XV:

Table XV

The data in Table XV indicate that: the reaction temperature is 35 ℃, the reaction time is 6 hours, the temperature is too low, the time is too long, the acidification is insufficient, the yield is low, and the purity is reduced; the reaction temperature is 75 ℃, the reaction time is 1 hour, the temperature is too high, the side reaction is increased, the yield is low, and the purity is low; the reaction temperature is 40-70 ℃, the reaction time is 1-6 hours, the yield is high, the purity is high, and the implementation effect is good;

example 4: preparation of tetrabromophenol tetrachloro-sulfonephthalein

1) 49.2g of 3,4,5, 6-tetrachlorophenol sulfophthalein is weighed, 150mL of acetic acid is added, and the mixture is heated and stirred at 45 ℃ until the mixture is homogeneous; 150mL of pure water is added, and the mixture is cooled to room temperature; adding 29mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 40.0g of liquid bromine, stirring, and controlling the temperature to be 55 ℃ for reaction for 5 hours; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, a filter cake is collected and dried, 76.5g of crude tetrabromophenol tetrachlorosulfophthalein is prepared, the yield is 94.7%, and the purity is 93.45%;

2) 76.5g of tetrabromophenol tetrachlorosulfonephthalein crude product prepared in the last step is added with 300mL of acetonitrile, 7.0g of lithium bicarbonate is added, and the mixture is stirred and reacted for 5 hours at the temperature of 45 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 72.4g of tetrabromophenol tetrachlorosulfonephthalein lithium salt, wherein the yield is 93.9% and the purity is 97.71%;

3) 72.4g of tetrabromophenol tetrachloro-sulfonephthalein lithium salt prepared in the previous step is added with 200mL of water, 10.8mL of acetic acid is added, and the mixture is stirred and reacted for 4 hours at the temperature of 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 66.7 g of pure tetrabromophenol tetrachlorosulfophthalein, wherein the yield is 92.8%, the total yield is 82.6%, and the purity is 99.17%;

example 5: preparation of tetrabromophenol tetrachloro-sulfonephthalein

1) 49.2g of 3,4,5, 6-tetrachlorophenol sulfophthalein is weighed, 100mL of acetic acid is added, and the mixture is heated and stirred at 60 ℃ until the mixture is homogeneous; adding 100mL of pure water, and cooling to room temperature; adding 30mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 38.5g of liquid bromine, stirring, and controlling the temperature to be 45 ℃ for reaction for 4 hours; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, a filter cake is collected and dried, 76.2g of tetrabromophenol tetrachlorosulfophthalein crude product is prepared, the yield is 94.3%, and the purity is 93.58%;

2) 76.2g of tetrabromophenol tetrachlorosulfophthalein crude product prepared in the last step is added with 300mL of acetonitrile, 8.5g of sodium bicarbonate is added, and the mixture is stirred and reacts for 3 hours at the temperature of 55 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 73.0g of tetrabromophenol tetrachloro-sulfonephthalein sodium salt, wherein the yield is 93.2% and the purity is 97.15%;

3) 73.0g of tetrabromophenol tetrachloro-sulfonephthalein sodium salt prepared in the previous step is added with 170mL of water, 10.6mL of acetic acid is added, and the mixture is stirred and reacted for 2 hours at the temperature of 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 65.9 g of pure tetrabromophenol tetrachlorosulfophthalein, wherein the yield is 92.8%, the total yield is 81.6%, and the purity is 99.32%;

example 6: preparation of tetrabromophenol tetrachloro-sulfonephthalein

1) 49.2g of 3,4,5, 6-tetrachlorophenol sulfophthalein is weighed, 200mL of acetic acid is added, and the mixture is heated and stirred at 55 ℃ until the mixture is homogeneous; 200mL of pure water is added and cooled to room temperature; adding 28mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 38.4g of liquid bromine, stirring, and controlling the temperature to be 55 ℃ for reaction for 4 hours; after the reaction, the reaction solution was cooled to room temperature, filtered, and the filter cake was collected and dried to obtain 75.9g of a crude tetrabromophenol tetrachlorosulfophthalein product, with a yield of 94.0% and a purity of 93.72%.

2) 75.9g of tetrabromophenol tetrachlorosulfonephthalein crude product prepared in the last step is added with 350mL of acetone, 9.5g of potassium bicarbonate is added, and the mixture is stirred and reacted for 4 hours at the temperature of 55 ℃; after the reaction is finished, crystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 74.4g of tetrabromophenol tetrachloro-sulfonephthalein potassium salt, wherein the yield is 93.5% and the purity is 97.74%;

3) 74.4g of tetrabromophenol tetrachloro-sulfonephthalein potassium salt prepared in the previous step is added with 300mL of water, 10.6mL of formic acid is added, and the mixture is stirred and reacted for 2 hours at the temperature of 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 65.8 g of pure tetrabromophenol tetrachlorosulfophthalein, wherein the yield is 92.6%, the total yield is 81.5%, and the purity is 99.12%;

example 7: preparation of tetrabromophenol tetrabromosulfonephthalein

1) 70.0g of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 350mL of acetic acid is added, and the mixture is heated and stirred at 45 ℃ until the mixture is homogeneous; 350mL of pure water is added, and the mixture is cooled to room temperature; adding 29mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 40g of liquid bromine, stirring, and controlling the temperature to be 55 ℃ for reaction for 5 hours; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, a filter cake is collected and dried to prepare 91.5g of tetrabromophenol tetrabromosulfonephthalein crude product, the yield is 92.8 percent, and the purity is 93.62 percent;

2) 91.5g of tetrabromophenol tetrabromosulfonephthalein crude product prepared in the previous step is added with 400mL of acetonitrile, 7.0g of lithium bicarbonate is added, and the mixture is stirred and reacted for 5 hours at the temperature of 45 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 85.8g of tetrabromophenol tetrabromosulfonephthalein lithium salt, wherein the yield is 93.2% and the purity is 97.57%;

3) 85.8g of tetrabromophenol tetrabromosulfonephthalein lithium salt prepared in the previous step is added with 300mL of water, 10.4mL of acetic acid is added, and the mixture is stirred and reacted for 4 hours at the temperature of 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 80.7 g of pure tetrabromophenol tetrabromosulfonephthalein product with the yield of 94.6%, the total yield of 81.9% and the purity of 99.27%;

example 8: preparation of tetrabromophenol tetrabromosulfonephthalein

1) 70.0g of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 200mL of acetic acid is added, and the mixture is heated and stirred at 45 ℃ until the mixture is homogeneous; 200mL of pure water is added and cooled to room temperature; adding 28mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 39g of liquid bromine, stirring, and controlling the temperature to be 45 ℃ for reaction for 5 hours; after the reaction, the reaction solution was cooled to room temperature, filtered, and the filter cake was collected and dried to obtain 92.8g of a crude tetrabromophenol tetrabromosulfonephthalein product, with a yield of 94.2% and a purity of 93.9%.

2) 92.8g of tetrabromophenol tetrabromosulfonephthalein crude product prepared in the previous step is added with 400mL of acetonitrile, 9.5g of sodium bicarbonate is added, and the mixture is stirred and reacted for 5 hours at the temperature of 45 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 88.5g of tetrabromophenol tetrabromo sulfophthalein sodium salt, wherein the yield is 93.1% and the purity is 97.5%;

3) 88.5g of tetrabromophenol tetrabromo sulfophthalein sodium salt prepared in the previous step is added with 500mL of water, 10.6mL of acetic acid is added, and the mixture is stirred and reacted for 6 hours at the temperature of 60 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 81.8 g of tetrabromophenol tetrabromosulfonephthalein pure product, wherein the yield is 94.5%, the total yield is 83.0%, and the purity is 99.52%;

example 9: preparation of tetrabromophenol tetrabromosulfonephthalein

1) 70.0g of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed, 200mL of acetic acid is added, and the mixture is heated and stirred at 45 ℃ until the mixture is homogeneous; 200mL of pure water is added and cooled to room temperature; adding 30mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 38g of liquid bromine, stirring, and controlling the temperature to be 45 ℃ for reaction for 5 hours; after the reaction, the reaction solution was cooled to room temperature, filtered, and the filter cake was collected and dried to obtain 91.3g of a crude tetrabromophenol tetrabromosulfonephthalein product, yield 92.6% and purity 93.32%.

2) Adding 91.3g of tetrabromophenol tetrabromosulfonephthalein crude product prepared in the previous step into 360mL of acetonitrile, adding 10.0g of potassium bicarbonate, stirring, and controlling the temperature to be 65 ℃ for reaction for 5 hours; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 88.3g of tetrabromophenol tetrabromosulfonephthalein potassium salt, wherein the yield is 93.1% and the purity is 97.81%;

3) 88.3g of tetrabromophenol tetrabromo sulfophthalein potassium salt prepared in the previous step is added with 360mL of water, 10.4mL of propionic acid is added, and the mixture is stirred and reacted for 6 hours at the temperature of 50 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 79.7 g of pure tetrabromophenol tetrabromosulfonephthalein product with the yield of 93.8%, the total yield of 80.9% and the purity of 99.41%;

example 10: preparation of tetrabromophenol tetraiodosulfonephthalein

1) 85.8g of 3,4,5, 6-tetraiodophenol sulfophthalein is weighed, 400mL of acetic acid is added, and the mixture is heated and stirred at 45 ℃ until the mixture is homogeneous; 400mL of pure water is added and cooled to room temperature; adding 30mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 38g of liquid bromine, stirring, and controlling the temperature to be 55 ℃ for reaction for 5 hours; after the reaction, the reaction solution was cooled to room temperature, filtered, and the filter cake was collected and dried to obtain 110.5g of crude tetrabromophenol tetraiodosulfonephthalein with a yield of 94.1% and a purity of 93.46%.

2) 110.5g of tetrabromophenol tetraiodosulfonephthalein crude product prepared in the previous step is added with 400mL of acetonitrile, 6.6g of lithium bicarbonate is added, and the mixture is stirred and reacted for 5 hours at the temperature of 45 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 103.8g of tetrabromophenol tetraiodosulfonephthalein lithium salt, wherein the yield is 93.5% and the purity is 97.65%;

3) 103.8g of tetrabromophenol tetraiodosulfonephthalein lithium salt prepared in the previous step is added with 300mL of water, 10.6mL of propionic acid is added, and the mixture is stirred and reacted for 4 hours at the temperature of 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 98.0 g of pure tetrabromophenol tetraiodosulfonephthalein, wherein the yield is 94.9%, the total yield is 83.5%, and the purity is 99.34%;

example 11: preparation of tetrabromophenol tetraiodosulfonephthalein

1) 85.8g of 3,4,5, 6-tetraiodophenol sulfophthalein is weighed, 400mL of acetic acid is added, and the mixture is heated and stirred at 55 ℃ until the mixture is homogeneous; 400mL of pure water is added and cooled to room temperature; adding 32mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 41g of liquid bromine, stirring, and controlling the temperature to be 55 ℃ for reaction for 5 hours; after the reaction, the reaction solution was cooled to room temperature, filtered, and the filter cake was collected and dried to obtain 110.5g of crude tetrabromophenol tetraiodosulfonephthalein with a yield of 94.2% and a purity of 93.29%.

2) 110.5g of tetrabromophenol tetraiodosulfonephthalein crude product prepared in the previous step is added with 340mL of acetonitrile, 8.0g of sodium bicarbonate is added, and the mixture is stirred and reacted for 6 hours at the temperature of 35 ℃; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 105.6g of tetrabromophenol tetraiodosulfonephthalein sodium salt, wherein the yield is 93.8% and the purity is 97.83%;

3) 105.6g of tetrabromophenol tetraiodosulfonephthalein sodium salt prepared in the previous step is added with 400mL of water, 10.6mL of formic acid is added, and the mixture is stirred and reacts for 4 hours at the temperature of 55 ℃; after the reaction is finished, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 97.3 g of pure tetrabromophenol tetraiodosulfonephthalein, wherein the yield is 93.9%, the total yield is 82.9%, and the purity is 99.15%;

example 12: preparation of tetrabromophenol tetraiodosulfonephthalein

1) 85.8g of 3,4,5, 6-tetraiodophenol sulfophthalein is weighed, 400mL of acetic acid is added, and the mixture is heated and stirred at 45 ℃ until the mixture is homogeneous; 400mL of pure water is added and cooled to room temperature; adding 30mL (35%) hydrogen peroxide, and uniformly stirring; slowly dripping 38g of liquid bromine, stirring, and controlling the temperature to be 55 ℃ for reaction for 5 hours; after the reaction is finished, the reaction solution is cooled to room temperature, filtered, a filter cake is collected and dried to prepare 111.0g of tetrabromophenol tetraiodosulfophthalein crude product, the yield is 94.6%, and the purity is 93.2%;

2) 111.0g of the tetrabromophenol tetraiodosulfonephthalein crude product prepared in the previous step is added with 400mL of acetonitrile, 10.5g of potassium bicarbonate is added, and the mixture is stirred and reacts for 5 hours at the temperature of 45 ℃; after the reaction is finished, crystallizing in the reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain 107.5g of tetrabromophenol tetraiodosulfonephthalein potassium salt, wherein the yield is 93.8% and the purity is 97.3%;

3) 107.5g of tetrabromophenol tetraiodosulfonephthalein potassium salt prepared in the previous step is added with 300mL of water, 10.6mL of acetic acid is added, and the mixture is stirred and reacted for 4 hours at the temperature of 55 ℃; after the reaction, recrystallizing in the reaction liquid, cooling to room temperature, filtering, collecting filter cakes, and drying to obtain 98.7 g of pure tetrabromophenol tetraiodosulfonephthalein with the yield of 94.8%, the total yield of 84.1% and the purity of 99.23%.

The above embodiments are merely illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solutions of the present invention should fall within the protection scope defined by the claims of the present invention without departing from the design spirit of the present invention.

Claims (10)

1. The preparation method is characterized in that 3,4,5, 6-tetrahalophenol sulfophthalein is taken as a raw material, and is oxidized and brominated with liquid bromine in aqueous solution with organic carboxylic acid to prepare a crude product of the tetrabromophenol tetrahalophthalein; then salifying with alkali metal salt in solvent, crystallizing to obtain tetrabromophenol tetrahalogen sulfophthalein alkali metal salt; then, the tetrabromophenol tetrahalosulfophthalein is subjected to acid conversion and recrystallization in an aqueous solution with organic carboxylic acid to obtain a tetrabromophenol tetrahalosulfophthalein pure product; the reaction formula is as follows:

Wherein X is Cl, br or I; m is Li, na or K;

the 3,4,5, 6-tetrahalophenol sulfophthalein is 3,4,5, 6-tetrachlorophenol sulfophthalein, 3,4,5, 6-tetrabromophenol sulfophthalein or 3,4,5, 6-tetraiodophenol sulfophthalein;

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 tetrabromophenol tetrahalosulfophthalein alkali metal salt is tetrabromophenol tetrachlorosulfophthalein alkali metal salt, tetrabromophenol tetrabromosulfophthalein alkali metal salt or tetrabromophenol tetraiodosulfophthalein alkali metal salt;

the tetrabromophenol tetrachloro-sulfonephthalein salt is tetrabromophenol tetrachloro-sulfonephthalein lithium salt, tetrabromophenol tetrachloro-sulfonephthalein sodium salt or tetrabromophenol tetrachloro-sulfonephthalein potassium salt; the tetrabromophenol tetrabromosulfonephthalein salt is tetrabromophenol tetrabromosulfonephthalein lithium salt, tetrabromophenol tetrabromosulfoephthalein sodium salt and tetrabromophenol tetrabromosulfoephthalein potassium salt; the tetrabromophenol tetraiodosulfonephthalein salt is tetrabromophenol tetraiodosulfonephthalein lithium salt, tetrabromophenol tetraiodosulfonephthalein sodium salt and tetrabromophenol tetraiodosulfonephthalein potassium salt;

the tetrabromophenol tetrahalosulfophthalein is tetrabromophenol tetrachlorosulfophthalein, tetrabromophenol tetrabromosulfophthalein or tetrabromophenol tetraiodosulfophthalein.

2. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 1, wherein the method comprises the following steps: the preparation method comprises the following specific steps:

2.1 Oxidation bromination): adding organic carboxylic acid with a certain mass-volume ratio into 3,4,5, 6-tetrahalophenol sulfophthalein (compound a), heating and stirring uniformly, adding water with a certain mass-volume ratio, cooling to room temperature, adding hydrogen peroxide with a certain mole ratio, stirring uniformly, adding liquid bromine with a certain mole ratio, stirring, and performing temperature control reaction; after the reaction is finished, cooling the reaction liquid to room temperature, filtering, recycling and applying the filtrate, collecting a filter cake, and drying to obtain a tetrabromophenol tetrahalogen sulfophthalein crude product (a compound b);

2.2 Salification and purification): adding an aprotic solvent with a certain mass-volume ratio into the tetrabromophenol tetrahalogen sulfophthalein crude product, adding alkali metal salt with a certain molar ratio, stirring, and performing temperature control reaction; after the reaction is finished, crystallizing in a reaction liquid, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain tetrabromophenol tetrahalogen sulfophthalein salt (a compound c);

2.3 Acid conversion purification: adding water with a certain mass volume ratio into tetrabromophenol tetrahalogen sulfophthalein salt, adding organic carboxylic acid with a certain molar ratio, stirring, and performing temperature control reaction; after the reaction is finished, recrystallizing in a reaction solution, cooling to room temperature, filtering, collecting a filter cake, and drying to obtain a pure tetrabromophenol tetrahalosulfophthalein (compound b);

The 3,4,5, 6-tetrahalophenol sulfophthalein is 3,4,5, 6-tetrachlorophenol sulfophthalein, 3,4,5, 6-tetrabromophenol sulfophthalein or 3,4,5, 6-tetraiodophenol sulfophthalein;

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 can be any one or two 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;

the tetrabromophenol tetrahalosulfophthalein salt is tetrabromophenol tetrachlorosulfophthalein alkali metal salt, tetrabromophenol tetrabromosulfophthalein alkali metal salt or tetrabromophenol tetraiodosulfophthalein alkali metal salt;

the tetrabromophenol tetrachloro-sulfonephthalein salt is tetrabromophenol tetrachloro-sulfonephthalein lithium salt, tetrabromophenol tetrachloro-sulfonephthalein sodium salt or tetrabromophenol tetrachloro-sulfonephthalein potassium salt; the tetrabromophenol tetrabromosulfonephthalein salt is tetrabromophenol tetrabromosulfonephthalein lithium salt, tetrabromophenol tetrabromosulfoephthalein sodium salt and tetrabromophenol tetrabromosulfoephthalein potassium salt; the tetrabromophenol tetraiodosulfonephthalein salt is tetrabromophenol tetraiodosulfonephthalein lithium salt, tetrabromophenol tetraiodosulfonephthalein sodium salt and tetrabromophenol tetraiodosulfonephthalein potassium salt;

The tetrabromophenol tetrahalosulfophthalein is tetrabromophenol tetrachlorosulfophthalein, tetrabromophenol tetrabromosulfophthalein or tetrabromophenol tetraiodosulfophthalein.

3. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 1, wherein the method comprises the following steps: in the oxidizing bromination step: the mass volume ratio of the 3,4,5, 6-tetrahalophenol sulfophthalein to the added organic carboxylic acid is 1:1-1:12; 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 sulfophthalein to the added water is 1:1-1:12; the molar ratio of the 3,4,5, 6-tetrabromophenol sulfophthalein to the added liquid bromine is 1:2-1:3; the molar ratio of the hydrogen peroxide to the 3,4,5, 6-tetrahalophenol sulfophthalein is 1:1-1:6; the molar ratio of the hydrogen peroxide to the liquid bromine is 1:1-1:2; the temperature of the temperature-controlled reaction is 20-70 ℃; the temperature control reaction time is 1-12 hours.

4. A process for the preparation of tetrabromophenol tetrahalosulfophthalein according to claim 3, wherein: the purity of the reaction initial raw material 3,4,5, 6-tetrahalophenol sulfophthalein is 90%, the yield of the tetrabromophenol tetrahalophthalein crude product prepared by oxidizing and brominating is 92%, and the purity is 93%.

5. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 1, wherein the method comprises the following steps: in the salification purification step: the dosage of the alkali metal salt is 1.0-1.5 eq of tetrabromophenol tetrahalogen sulfophthalein; the alkali metal salt selected is bicarbonate, preferably lithium bicarbonate, sodium bicarbonate or potassium bicarbonate; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein crude product to the aprotic solvent is 1:2-1:12 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 control reaction is 30-70 ℃; the reaction time is 1-12 hours.

6. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 5, wherein: the tetrabromophenol tetrahalosulfophthalein alkali metal salt is crystallized by a self-reaction system through salification reaction, and the yield of the obtained tetrabromophenol tetrahalosulfophthalein alkali metal salt is 93 percent, and the purity is 97.0 percent.

7. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 1, wherein the method comprises the following steps: in the acid conversion purification step: the molar ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added organic carboxylic acid is 1:1-1:6; the organic carboxylic acid is one of formic acid, acetic acid or propionic acid; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added water is 1:1-1:12 mL; the temperature control reaction temperature is 35-90 ℃; the reaction time of temperature control is 1-12 hours.

8. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 7, wherein: the pure tetrabromophenol tetrahalosulfophthalein is recrystallized by an autoreaction system through acid conversion reaction, and the yield of the obtained pure tetrabromophenol tetrahalosulfophthalein is 94% and the purity is 99.0%.

9. A process for the preparation of tetrabromophenol tetrahalosulfophthalein according to claim 3, wherein:

in the oxidizing and brominating step, the mass volume ratio of the 3,4,5, 6-tetrahalophenol sulfophthalein to the added carboxylic acid is 1:2-1:6; the mass volume ratio of the 3,4,5, 6-tetrahalophenol sulfophthalein to the added water is 1 g:2-6 mL; the molar ratio of the 3,4,5, 6-tetrabromophenol sulfophthalein to the added liquid bromine is 1:2-1:3; the molar ratio of the hydrogen peroxide to the 3,4,5, 6-tetrahalophenol sulfophthalein is 1:1-1:6; the molar ratio of the hydrogen peroxide to the liquid bromine is 1:1-1:2; the temperature of the temperature-controlled reaction is 25-60 ℃; the temperature control reaction time is 1-6 hours;

In the salifying purification step, the mass volume ratio of the crude tetrabromophenol tetrahalogen sulfophthalein to the aprotic solvent is 1:2-1:6; the aprotic solvent is one of acetone, acetonitrile, dioxane, ethyl acetate or dichloromethane; the temperature control reaction is carried out at 35-65 ℃; the reaction time is 1-6 hours;

in the acid conversion purification step, the molar ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added organic carboxylic acid is 1:2-1:4; the mass volume ratio of the tetrabromophenol tetrahalogen sulfophthalein salt to the added water is 1:2-1:6; the temperature of the temperature-controlled reaction is 40-70 ℃; the reaction time of temperature control is 1-6 hours.

10. The method for preparing tetrabromophenol tetrahalosulfophthalein according to claim 9, wherein: the first purification is completed through oxidation bromination, the second purification is completed through crystallization by an aprotic solvent used for salification, the third purification is completed through recrystallization by a carboxylic acid aqueous solution used for acid conversion, and finally the purity of the obtained tetrabromophenol tetrahalosulfophthalein alkali metal salt product is more than 80 percent and more than 99.0 percent.