Aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein

Abstract

The invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, which belongs to the technical field of chemical drug synthesis. 3,4,5,6-tetrahalophenol sulfonphthalein alkali metal salt is used as a raw material, and is subjected to oxidation bromination in an aqueous phase, and crystallization is performed by a reaction solution after acid adjustment to obtain a crude tetrabromophenol tetrahalosulfonphthalein product, and then recrystallization is performed by an aprotic solvent to obtain a pure tetrabromophenol tetrahalosulfonphthalein product. The invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, and compared with the prior art, the synthesis method has high yield, high purity, low cost, and a simple synthesis method, mild conditions, environmental friendliness, and is beneficial to mass production, and is suitable for large-scale promotion and application.

Description

Technical Field

[0001] The invention relates to the technical field of chemical drug synthesis, in particular to a method for synthesizing tetrabromophenol tetrahalosulfonphthalein. Background Art

[0002] Tetrabromo phenol tetrahalogenated suofonephthalein (TBPTHSP) belongs to the sulfonphthalein class of compounds. This class of compounds has high stability and good color fixation effect, and has become an important class of dyes. In addition, this class of compounds has high sensitivity and has become an important acid-base indicator or protein error indicator in clinical diagnosis. Its structural formula is as follows:

[0003]

[0004] In formula (1), X can be Cl, Br or I;

[0005] The conventional synthesis method of tetrabromophenol tetrahalosulfonphthalein is to use tetrahalophenol sulfonphthalein (phenol tetrahalosulfonphthalein) as raw material, and glacial acetic acid as solvent, and to obtain it by bromination reaction. The method uses a large amount of liquid bromine, and a large amount of hydrogen bromide produced in the reaction process can only be disposed of, which wastes reagents, and a large amount of glacial acetic acid also needs neutralization treatment, which is unfriendly to the environment. In addition, the reaction method is difficult to carry out thoroughly, and the product impurities are high, purification is difficult, the yield is low, the purity is low, the cost is high, and it is difficult to mass production.

[0006] Therefore, how to develop a synthesis method of tetrabromophenol tetrahalosulfonphthalein with high yield, high purity, low cost, environmental friendliness and beneficial to industrial production is a technical problem that needs to be solved at present. Summary of the invention

[0007] The purpose of the present invention is to overcome the deficiencies of the prior art and provide an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein which is simple to operate, has high yield, high purity, low cost and is beneficial to industrial production. To achieve the above purpose, the present invention provides the following technical solutions:

[0008] To achieve the above object, the present invention provides the following technical solutions:

[0009] The invention provides a method for synthesizing tetrabromophenol tetrahalosulfonphthalein in an aqueous phase. The method comprises the following steps: using 3,4,5,6-tetrahalophenol sulfonphthalein alkali metal salt as a raw material, oxidizing and brominating the raw material with liquid bromine in an aqueous phase through hydrogen peroxide, crystallizing the raw material in an acid-adjusted reaction solution to obtain a crude tetrabromophenol tetrahalosulfonphthalein product, and then recrystallizing the raw material in an aprotic solvent to obtain a pure tetrabromophenol tetrahalosulfonphthalein product.

[0010] The reaction formula of the synthetic method is as follows:

[0011]

[0012] In formula (1), M is Li, Na or K; and X is Cl, Br or I.

[0013] The 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt is 3,4,5,6-tetrahalophenolsulfonphthalein lithium salt, 3,4,5,6-tetrahalophenolsulfonphthalein sodium salt or 3,4,5,6-tetrahalophenolsulfonphthalein potassium salt.

[0014] The 3,4,5,6-tetrahalophenolsulfonphthalein is 3,4,5,6-tetrachlorophenolsulfonphthalein, 3,4,5,6-tetrabromophenolsulfonphthalein or 3,4,5,6-tetraiodophenolsulfonphthalein.

[0015] A method for synthesizing tetrabromophenol tetrahalosulfonphthalein in an aqueous phase, comprising the following steps:

[0016] 1) Oxidative bromination: add water in a certain mass volume ratio to 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt, stir evenly; add liquid bromine in a certain molar ratio, stir evenly; add hydrogen peroxide in a certain molar ratio, stir and react at controlled temperature to obtain a reaction solution;

[0017] 2) Crystallization: add an appropriate amount of organic carboxylic acid to the reaction solution, heat and stir, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrahalosulfonphthalein product;

[0018] 3) Recrystallization: Add a non-protonic solvent in a certain mass volume ratio to the crude tetrabromophenol tetrahalosulfonphthalein, heat and control the temperature with stirring, cool to room temperature, filter, collect the filter cake, and dry to obtain the pure tetrabromophenol tetrahalosulfonphthalein;

[0019] The present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, in which in the oxidation bromination step:

[0020] The mass volume ratio of the 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt to water is 1:5 to 1:15;

[0021] The molar ratio of 3,4,5,6-tetrahalophenolsulfonphthalein to liquid bromine is 1:2 to 1:3;

[0022] The molar ratio of 3,4,5,6-tetrahalophenolsulfonphthalein to hydrogen peroxide is 1:2 to 1:4;

[0023] The temperature of the temperature control reaction is 20°C to 50°C; the temperature control reaction time is 2 to 12 hours;

[0024] The present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, in which in the crystallization step:

[0025] The organic carboxylic acid is one of formic acid, acetic acid or propionic acid;

[0026] The molar ratio of the 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal to the organic carboxylic acid is 1:1 to 1:3;

[0027] The heating temperature is 50°C to 80°C; the temperature control time is 2 to 12 hours;

[0028] The present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, wherein in the recrystallization step:

[0029] The solvent is an aprotic solvent, specifically any one or a combination of two of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, and isobutyl ether;

[0030] Furthermore, the aprotic solvent is one of tetrahydrofuran, acetone, acetonitrile, ethyl acetate, dichloromethane, chloroform, petroleum ether, n-propyl ether, and isopropyl ether;

[0031] The mass volume ratio of the crude tetrabromophenol tetrahalosulfonphthalein to the aprotic solvent is 1:2 to 1:10;

[0032] The heating temperature is 35°C to 80°C; the temperature control time is 1 to 24 hours;

[0033] Furthermore, the heating temperature is 40°C to 75°C; the temperature control time is 2 to 12 hours;

[0034] The present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, wherein in the oxidative bromination step:

[0035] The mass volume ratio of tetrabromophenol tetrahalosulfonphthalein alkali metal salt to water is 1:5, the reaction raw materials are well dispersed, and the reaction is relatively complete;

[0036] The liquid bromine used in the bromination reaction is more than 2 times the equivalent of the tetrahalosulfonphthalein alkali metal salt, and the reaction can be completed, which is much lower than at least 4 times the equivalent in the previous technology, thus saving a large amount of liquid bromine;

[0037] The hydrogen peroxide used in the oxidation reaction is more than 2 times the equivalent of tetrahalosulfonphthalein alkali metal salt, which can completely oxidize the hydrogen bromide produced by the reaction. If it exceeds 4 times the equivalent, it is easy to cause side reactions;

[0038] If the temperature of the temperature control reaction is lower than 20°C, the reaction will be too slow; if the reaction temperature is higher than 50°C, side reactions will easily occur, affecting the yield and purity.

[0039] The temperature control reaction time is 1 hour, the reaction is not complete, and the reaction time is 13 hours, and the by-product generation begins to increase;

[0040] The present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, wherein in the crystallization step:

[0041] When the acid selected is an organic carboxylic acid, it is conducive to the formation of tetrabromophenol tetrahalosulfonphthalein, and the resulting crystallization mother solution has a better crystallization effect; when other acids are selected, tetrabromophenol tetrahalosulfonphthalein has a darker color, is difficult to filter, and has a poor crystallization effect;

[0042] The selected organic carboxylic acid is added in too low an equivalent amount, the acidification is not sufficient, the yield is low, the purity is low, and the addition ratio is too high, which wastes reagents;

[0043] The crystallization temperature is above 50°C, which can ensure sufficient crystallization and achieve better results. If the crystallization temperature exceeds 80°C, side reactions may occur easily.

[0044] If the temperature control time is less than 2 hours, the crystallization is not sufficient; if the temperature control time is more than 12 hours, impurities increase;

[0045] The invention uses the self-reaction system for crystallization, so that the large polar impurities are fully retained in the crystallization mother liquor, and can be separated and removed, and the purity of the obtained tetrabromophenol tetrahalosulfonphthalein crude product reaches 97%.

[0046] The present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, wherein in the recrystallization step:

[0047] When the solvent used for recrystallization is a protic solvent, it will cause a color reaction of tetrabromophenol tetrahalosulfonphthalein, and the color of the product is too dark; when an aprotic solvent is used, the color is lighter; the aprotic solvent is one of acetonitrile, ethyl acetate, dichloromethane, chloroform, ether, petroleum ether, n-propyl ether, and isopropyl ether;

[0048] When the volume of the aprotic solvent is too small compared with the crude tetrabromophenol tetrahalosulfonphthalein, the recrystallization is insufficient and the purity is low; when the volume of the aprotic solvent is too large compared with the crude tetrabromophenol tetrahalosulfonphthalein, the yield is low; the mass volume ratio of the crude tetrabromophenol tetrahalosulfonphthalein to the aprotic solvent is 1:1 to 1:12, the yield is high, the purity is high and the effect is good;

[0049] When the recrystallization temperature is lower than 40°C, the reaction is not sufficient; when the temperature is higher than 75°C, side reactions are easily induced and the color of the product deepens;

[0050] The recrystallization time is less than 1 hour, the reaction is not complete, the yield is low, the purity is low, and the free impurities are high; the reaction time is greater than 12 hours, the reaction time is too long, there are many side reactions, the impurities are high, and the purity is low;

[0051] The invention uses recrystallization to dissolve low polar molecules in tetrabromophenol tetrahalosulfonphthalein in the recrystallization mother liquor, while tetrabromophenol tetrahalosulfonphthalein is difficult to dissolve in the crystallization solvent, thereby realizing separation of the product and impurities and achieving purification effect. The purity of the prepared tetrabromophenol tetrahalosulfonphthalein reaches more than 99%.

[0052] The invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein. The method takes 3,4,5,6-tetrahalophenol sulfonphthalein alkali metal salt as a raw material, performs oxidation bromination in an aqueous phase, and crystallizes a reaction solution after acid adjustment to obtain a crude tetrabromophenol tetrahalosulfonphthalein product. The crude tetrabromophenol tetrahalosulfonphthalein product is then recrystallized in an aprotic solvent to obtain a pure tetrabromophenol tetrahalosulfonphthalein product.

[0053] The invention provides a method for synthesizing tetrabromophenol tetrahalosulfonphthalein in an aqueous phase. The method uses 3,4,5,6-tetrahalophenol sulfonphthalein alkali metal salt (with a purity of 95%) as a raw material, improves reaction efficiency through oxidation bromination in an aqueous phase, greatly reduces the amount of liquid bromine used and reduces costs, and is environmentally friendly. The method is crystallized in a self-reaction system and then recrystallized in a non-proton solvent, so that the purity of the prepared tetrabromophenol tetrahalosulfonphthalein salt reaches 99% and the total yield reaches 85%.

[0054] Compared with the prior art, the present invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein, which has the following beneficial effects:

[0055] The invention provides an aqueous phase synthesis method of tetrabromophenol tetrahalosulfonphthalein. The synthesis method has high yield, high purity and low cost, and the synthesis method is simple, mild in conditions, environmentally friendly, beneficial to mass production and suitable for large-scale promotion and application. The method comprises the following steps: first purification is completed by oxidative bromination, second purification is completed by crystallization through an aprotic solvent used for salt formation, and third purification is completed by recrystallization through a carboxylic acid aqueous solution used for acid conversion. The total yield of the tetrabromophenol tetrahalosulfonphthalein product finally prepared is more than 80%, and the purity is more than 99.0%. DETAILED DESCRIPTION

[0056] The technical solution of the present invention will be described clearly and completely through specific implementation methods. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0057] The 3,4,5,6-tetrahalophenolsulfonphthalein lithium salt, 3,4,5,6-tetrahalophenolsulfonphthalein sodium salt or 3,4,5,6-tetrahalophenolsulfonphthalein potassium salt used in the present invention has a purity of more than 95%.

[0058] Example 1: Comparison of the effects of the oxidation bromination process

[0059] (1) Selection of water addition ratio

[0060] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water according to the mass volume ratio of 1:4, 1:5, 1:10, 1:15, 1:16 respectively, add 2.2 eq of liquid bromine respectively, stir, add 2.2 eq of hydrogen peroxide respectively, stir, control the temperature at 40°C to react for 2 hours, stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 60°C to react for 3 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 1:

[0061] Table 1 Selection of water addition ratio

[0062]

[0063] The data in Table 1 show that when the water addition ratio is lower than 1:4 or higher than 1:16, the yield and purity decrease; when the water addition ratio is 1:5 to 1:15, the yield and purity are higher.

[0064] (2) Selection of liquid bromine feed equivalent

[0065] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water according to a mass volume ratio of 1:10, add 1.9, 2.0, 2.5, 3.0, and 3.1 eq of liquid bromine respectively, stir, add 3.1 eq of hydrogen peroxide respectively, stir, control the temperature at 40°C to react for 2 hours, stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 60°C to react for 3 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 2:

[0066] Table 2 Selection of liquid bromine feed equivalent

[0067]

[0068]

[0069] The data in Table 2 show that: the liquid bromine feed of 1.9eq is too low, the yield is low, and the purity is low; the liquid bromine feed amount is 2.0 to 3.0eq, the purity and yield are significantly higher; the liquid bromine feed is 3.1eq, the yield does not increase, and the purity begins to decrease; it can be seen that the implementation effect is better when the liquid bromine feed is between 2.0 and 3.0eq;

[0070] (3) Selection of hydrogen peroxide feed equivalent

[0071] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water according to a mass volume ratio of 1:10, add 2.0 eq of liquid bromine respectively, stir, add 1.9, 2.0, 3.0, 4.0, 4.1 eq of hydrogen peroxide respectively, stir evenly, then control the temperature at 40°C to react for 2 hours, stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 50°C to react for 3 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 3:

[0072] Table 3 Selection of hydrogen peroxide feed equivalent

[0073]

[0074] The data in Table 3 show that: the amount of hydrogen peroxide added is too small, 1.9 eq, and the hydrogen bromide produced cannot be completely oxidized, resulting in low yield and low purity; the amount of hydrogen peroxide added is 2.0-4.0 eq, and the purity and yield are relatively high. When the amount of hydrogen peroxide added reaches 4.1 eq, the yield and purity decrease;

[0075] (4) Selection of reaction temperature

[0076] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water at a mass volume ratio of 1:8, stir, add 3.0 eq of liquid bromine respectively, stir, add 4.0 eq of hydrogen peroxide respectively, stir, control the temperature at 15°C, 20°C, 35°C, 50°C, and 55°C respectively to react for 12 hours, stop the reaction; add 1 equivalent of acetic acid, heat and control the temperature at 70°C to react for 3 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 4:

[0077] Table 4 Selection of reaction temperature

[0078]

[0079] The data in Table 4 show that: the reaction temperature is 15°C, which is too low, the reaction is incomplete, the yield is low, and the purity is low; the reaction temperature is 55°C, the reaction is too violent, there are many by-products, and the yield and purity are reduced; the reaction temperature is 20°C to 50°C, the reaction yield is high, and the purity is high;

[0080] (5) Choice of reaction time

[0081] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water at a mass volume ratio of 1:10, stir, add 3.0 eq of liquid bromine respectively, stir, add 4.0 eq of hydrogen peroxide respectively, stir, control the temperature at 40°C to react for 1 hour, 2 hours, 7 hours, 12 hours, and 13 hours respectively, stop the reaction; add 1 equivalent of acetic acid, heat and control the temperature at 80°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 5:

[0082] Table 5 Selection of reaction time

[0083]

[0084] The data in Table 5 show that: the temperature control time of 1 hour is too short, the reaction is not sufficient, the yield is low, and the purity is low; the temperature control time is 13 hours, the time is too long, and the purity decreases; the reaction time is 2 to 12 hours, the yield is high, and the purity is high;

[0085] Example 2: Comparison of the effects of implementation during crystallization

[0086] (1) Selection of organic carboxylic acid

[0087] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water at a mass volume ratio of 1:10 respectively, stir, add 2.5 eq of liquid bromine respectively, stir, add 3.0 eq of hydrogen peroxide respectively, stir, control the temperature at 40°C for 7 hours, stop the reaction; add 1 eq of formic acid, acetic acid, and propionic acid respectively, heat and control the temperature at 80°C for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 6:

[0088] Table 6 Selection of organic carboxylic acids

[0089]

[0090] The data in Table 6 show that the yield and purity of the three organic carboxylic acids, formic acid, acetic acid or propionic acid, are significantly higher than butyric acid, and the purity of hydrochloric acid is the lowest;

[0091] (2) Selection of organic carboxylic acid equivalents

[0092] Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, weigh 5 portions respectively, add water at a mass volume ratio of 1:10, stir, add 2.5 eq of liquid bromine respectively, stir, add 3.0 eq of hydrogen peroxide respectively, stir, control the temperature at 40 ° C for 7 hours, stop the reaction; add 0.9 eq, 1.0 eq, 2.0, 3.0 eq, 3.1 eq of propionic acid respectively, heat and control the temperature at 70 ° C for 4 hours, cool to room temperature and filter,

[0093] The filter cake was collected and dried to obtain the crude product of tetrabromophenol tetrabromosulfonphthalein. The relevant experimental data are shown in Table 7.

[0094] Table 7 Selection of organic carboxylic acid equivalents

[0095]

[0096]

[0097] The data in Table 7 show that: when the propionic acid feed ratio is 0.9 eq, the acidification is insufficient, the yield is too low, and the purity is low; when the propionic acid feed ratio is 3.1 eq, the yield is reduced; when the acetic acid feed ratio is 1.0 to 3.0 eq, the yield is high and the purity is high;

[0098] (3) Selection of crystallization temperature and time

[0099] The crude tetrabromophenol tetrabromosulfonphthalein obtained in the previous step was weighed in 5 portions, each portion was 98.6 g (0.1 mol), acetonitrile was added in a mass volume ratio of 1:3, 1.1 ep of sodium bicarbonate was added, and the mixture was stirred and reacted at 30, 35, 55, 65, and 70°C respectively; after the reaction was completed, the mixture was crystallized in the reaction solution, cooled to room temperature, filtered, the filter cake was collected, and dried to obtain tetrabromophenol tetrabromosulfonphthalein sodium salt. The relevant experimental data are shown in Table 7:

[0100] Table 7 Selection of crystallization temperature and time

[0101]

[0102] The data in Table 7 show that: when the reaction temperature is 45°C and the reaction time is 12 hours, the yield is low and the purity is low; when the reaction time is 85°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 50 to 80°C and the reaction time is 2 to 12 hours, the yield is high and the purity is high;

[0103] Example 3: Comparison of the effects of implementation during recrystallization

[0104] Weigh 2075.7 g (3.0 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, add water according to a mass volume ratio of 1:15, stir, add 2.5 eq of liquid bromine, stir, add 3.0 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 6 hours, stop the reaction, add 2.0 eq of acetic acid, heat and control the temperature at 75°C to react for 3 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 2723.0 g of crude tetrabromophenol tetrabromosulfonphthalein with a yield of 92.1% and a purity of 93.15%, which is used in the following experiments;

[0105] (1) Selection of recrystallization solvent

[0106] Weigh 10 portions of the crude tetrabromophenol tetrabromosulfonphthalein obtained in the previous step, each portion is 100 g, and tetrahydrofuran, acetone, acetonitrile, ethyl acetate, dichloromethane, chloroform, petroleum ether, n-propyl ether, isopropyl ether, and any other solvent are added in a mass volume ratio of 1:5, respectively, and stirred, and the temperature is controlled at 40°C to react for 10 hours; after the reaction is completed, cool to room temperature, filter, collect the filter cake, and dry to obtain tetrabromophenol tetrabromosulfonphthalein sodium salt. The relevant experimental data are shown in Table 8:

[0107] Table 8 Selection of recrystallization solvent

[0108]

[0109] The data in Table 8 show that the yield and purity are higher when tetrahydrofuran, acetone, acetonitrile, ethyl acetate, dichloromethane, chloroform, petroleum ether, n-propyl ether, and isopropyl ether are selected as the recrystallization solvent; the yield and purity are lower when carbon tetrachloride or other solvents are selected;

[0110] (2) Selection of the recrystallization solvent feed ratio

[0111] The crude tetrabromophenol tetrabromosulfonphthalein obtained in the previous step was weighed in 5 portions, each 100 g, and acetonitrile was added according to the mass volume ratio of 1:1, 1:2, 1:6, 1:10, and 1:11, respectively, and the temperature was controlled at 50°C and stirred for 4 hours; after the reaction was completed, crystallization was carried out in the reaction solution, cooled to room temperature, filtered, the filter cake was collected, and dried to obtain tetrabromophenol tetrabromosulfonphthalein sodium salt. The relevant experimental data are shown in Table 9:

[0112] Table 9 Selection of Recrystallization Solvent Feeding Ratio

[0113]

[0114] The data in Table 9 show that when the mass volume ratio of the recrystallization solvent is 1:1, the reaction is insufficient, the yield is low, and the purity is low; when the mass volume ratio is 1:11, the system is too large, the yield is low, and the solvent is wasted; when the mass volume ratio is selected within the range of 1:2 to 1:10, the yield is high and the purity is high;

[0115] (3) Selection of recrystallization temperature and time

[0116] Weigh 5 portions of the crude tetrabromophenol tetrabromosulfonphthalein obtained in the previous step, 98.6 g (0.1 mol) each, add acetonitrile at a mass volume ratio of 1:3, stir, and react at the temperature and time in Table 10, cool to room temperature, filter, collect the filter cake, and dry to obtain tetrabromophenol tetrabromosulfonphthalein sodium salt. The relevant experimental data are shown in Table 10:

[0117] Table 10 Selection of recrystallization temperature and time

[0118]

[0119] The data in Table 10 show that: when the reaction temperature is 35°C and the reaction time is 13 hours, the temperature is too low, the time is too long, the yield is low, and the purity is low; when the reaction time is 80°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 to 75°C and the reaction time is 2 to 12 hours, the yield is high and the purity is high;

[0120] Example 4: Synthesis of Tetrabromophenol Tetrachlorosulfonphthalein

[0121] Weigh 49.8 g (0.1 mol) of 3,4,5,6-tetrachlorophenolsulfonphthalein lithium salt, add water at a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 75.2 g of tetrabromophenol tetrachlorosulfonphthalein crude product, with a yield of 93.1% and a purity of 97.34%;

[0122] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 69.1 g of tetrabromophenol tetrachlorosulfonphthalein, with a total yield of 85.6% and a purity of 99.41%;

[0123] Example 5: Synthesis of Tetrabromophenol Tetrachlorosulfonphthalein

[0124] 1) Weigh 51.4 g (0.1 mol) of 3,4,5,6-tetrachlorophenolsulfonphthalein sodium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 75.0 g of tetrabromophenol tetrachlorosulfonphthalein crude product, with a yield of 92.9% and a purity of 97.65%;

[0125] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 69.0 g of tetrabromophenol tetrachlorosulfonphthalein, with a total yield of 85.4% and a purity of 99.27%;

[0126] Example 6: Synthesis of Tetrabromophenol Tetrachlorosulfonphthalein

[0127] 1) Weigh 53.0 g (0.1 mol) of 3,4,5,6-tetrachlorophenolsulfonphthalein potassium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 75.7 g of tetrabromophenol tetrachlorosulfonphthalein crude product, with a yield of 93.7% and a purity of 97.31%;

[0128] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 69.5 g of tetrabromophenol tetrachlorosulfonphthalein, with a total yield of 86.1% and a purity of 99.71%;

[0129] Example 7: Synthesis of Tetrabromophenol Tetrabromosulfonphthalein

[0130] 1) Weigh 67.6 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein lithium salt, add water at a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 91.8 g of tetrabromophenol tetrabromosulfonphthalein crude product, with a yield of 93.2% and a purity of 97.55%;

[0131] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 84.1 g of tetrabromophenol tetrabromosulfonphthalein, with a total yield of 85.3% and a purity of 99.39%;

[0132] Example 8: Synthesis of Tetrabromophenol Tetrabromosulfonphthalein

[0133] 1) Weigh 69.2 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 76.5 g of tetrabromophenol tetrabromosulfonphthalein crude product, with a yield of 92.8% and a purity of 97.21%;

[0134] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 72.4 g of tetrabromophenol tetrabromosulfonphthalein, with a total yield of 85.4% and a purity of 99.77%;

[0135] Example 9: Synthesis of Tetrabromophenol Tetrabromosulfonphthalein

[0136] 1) Weigh 70.8 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein potassium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 92.0 g of tetrabromophenol tetrabromosulfonphthalein crude product, with a yield of 93.4% and a purity of 97.11%;

[0137] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 84.4 g of tetrabromophenol tetrabromosulfonphthalein, with a total yield of 85.6% and a purity of 99.66%;

[0138] Example 10: Synthesis of Tetrabromophenol Tetraiodosulfonphthalein

[0139] 1) Weigh 86.4 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein lithium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 109.8 g of tetrabromophenol tetraiodosulfonphthalein crude product, with a yield of 93.6% and a purity of 97.78%;

[0140] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 101.0 g of tetrabromophenol tetraiodosulfonphthalein with a total yield of 86.1% and a purity of 99.41%;

[0141] Example 11: Synthesis of Tetrabromophenol Tetraiodosulfonphthalein

[0142] 1) Weigh 88.0 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein sodium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 108.9 g of tetrabromophenol tetraiodosulfonphthalein crude product, with a yield of 92.8% and a purity of 97.34%;

[0143] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 100.7 g of tetrabromophenol tetraiodosulfonphthalein, with a total yield of 85.8% and a purity of 99.17%;

[0144] Example 12: Synthesis of Tetrabromophenol Tetraiodosulfonphthalein

[0145] 1) Weigh 89.6 g (0.1 mol) of 3,4,5,6-tetrabromophenolsulfonphthalein potassium salt, add water according to a mass volume ratio of 1:10, stir, add 2.2 eq of liquid bromine, stir, add 2.5 eq of hydrogen peroxide, stir, control the temperature at 45°C to react for 7 hours, and stop the reaction; add 1 eq of acetic acid, heat and control the temperature at 75°C to react for 2 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 108.8 g of tetrabromophenol tetraiodosulfonphthalein crude product, with a yield of 92.7% and a purity of 97.53%;

[0146] 2) Add 300 mL of acetonitrile to the product obtained in the previous step, stir, heat and control the temperature at 45° C. and stir for 5 hours, cool to room temperature, filter, collect the filter cake, and dry to obtain 100.2 g of tetrabromophenol tetraiodosulfonphthalein with a yield of 85.4% and a purity of 99.82%;

[0147] The embodiments described above are merely descriptions of preferred implementation modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the scope of protection determined by the claims of the device of the present invention.

Claims

1. A method for synthesizing tetrabromophenol tetrahalosulfonphthalein in aqueous phase, characterized in that: Using 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt as raw material, oxidizing and brominating with liquid bromine in water phase by hydrogen peroxide, crystallizing in the reaction solution after acid adjustment to obtain crude tetrabromophenol tetrahalosulfonphthalein, and then recrystallizing in a non-protonic solvent to obtain pure tetrabromophenol tetrahalosulfonphthalein; The reaction formula of the synthesis method is as follows: In formula (1), M is Li, Na or K; and X is Cl, Br or I.

2. The method according to claim 1, characterized in that The 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt is one of 3,4,5,6-tetrahalophenolsulfonphthalein lithium salt, 3,4,5,6-tetrahalophenolsulfonphthalein sodium salt or 3,4,5,6-tetrahalophenolsulfonphthalein potassium salt.

3. The method according to claim 2, characterized in that The halogen element in the 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt is chlorine, bromine or iodine.

4. The method according to claim 1, characterized in that: The tetrabromophenol tetrahalosulfonphthalein is tetrabromophenol tetrachlorosulfonphthalein, tetrabromophenol tetrabromosulfonphthalein or tetrabromophenol tetraiodosulfonphthalein.

5. The method according to claim 1, characterized in that The specific steps of the synthesis method are as follows: 1) Oxidative bromination: add water in a certain mass volume ratio to 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt, stir evenly; add liquid bromine in a certain molar ratio, stir evenly; add hydrogen peroxide in a certain molar ratio, stir and react at controlled temperature to obtain a reaction solution; 2) Crystallization: add an appropriate amount of organic carboxylic acid to the reaction solution, heat and stir, cool to room temperature, filter, collect the filter cake, and dry to obtain a crude tetrabromophenol tetrahalosulfonphthalein product; 3) Recrystallization: Add a certain mass volume ratio of aprotic solvent to the crude tetrabromophenol tetrahalosulfonphthalein, heat and control the temperature with stirring, cool to room temperature, filter, collect the filter cake, and dry to obtain the pure tetrabromophenol tetrahalosulfonphthalein.

6. The method according to claim 5, characterized in that The temperature of the temperature-controlled reaction in step 1) is 20° C. to 50° C., and the temperature-controlled reaction time is 2 to 12 hours.

7. The method according to claim 5, characterized in that In the step 2), the organic carboxylic acid is any one of formic acid, acetic acid or propionic acid; and the molar ratio of 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal to the organic carboxylic acid is 1:1 to 1:

3.

8. The method according to claim 5, characterized in that In the step 3), the aprotic solvent is any one of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, and isobutyl ether, or a combination of two thereof.

9. The method according to any one of claims 1 to 8, characterized in that: The purity of the tetrabromophenol tetrahalosulfonphthalein reaches 99%, and the total yield reaches 85%.

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