An alkali metal salt of tetrabromophenol blue, its preparation method and application

Abstract

The present invention provides a tetrabromophenol blue alkali metal salt, a preparation method and an application thereof, belonging to the technical field of tetrabromophenol blue salt formation. The tetrabromophenol blue alkali metal salt described in the present invention is a tetrabromophenol blue lithium salt, a tetrabromophenol blue sodium salt and a tetrabromophenol blue potassium salt; the preparation method of the tetrabromophenol blue alkali metal salt is: carrying out a salt formation reaction between tetrabromophenol blue and an alkali metal salt in an aprotic solvent, crystallizing to obtain a crude product, and then performing recrystallization in an aprotic solvent to obtain a pure product of the tetrabromophenol blue alkali metal salt. The preparation method of the tetrabromophenol blue alkali metal salt provided by the present invention overcomes the problem of poor water solubility of the existing tetrabromophenol blue, and the preparation process method is simple, the conditions are mild, the product purity is high, the yield is high, the cost is low, and it can be mass-produced, which is beneficial to further application in albumin diagnostic reagents and hair dyes.

Description

Technical Field

[0001] The present invention relates to the technical field of the salification of tetrabromophenol blue, and particularly relates to an alkali metal salt of tetrabromophenol blue, a preparation method thereof, and an application thereof. Background Art

[0002] Tetrabromophenol blue (TBPB), chemical name: 4,5,6,7-tetrabromo-3,3-bis(3,5-dibromo-4-hydroxyphenyl)-o-sulfobenzoic anhydride, and its structural formula is as follows:

[0003]

[0004] Tetrabromophenol blue has two main uses. One is that because of its high sensitivity, it is used as a protein error indicator in clinical diagnostic reagents; the other is that because of its good color fixation effect, it is often used in hair dyes. However, since tetrabromophenol blue is insoluble in water, in clinical diagnostic reagents, a large amount of organic solvents are often used for dissolution, wasting reagents and increasing costs; in addition, when used in hair dyes, due to its extremely low water solubility, organic solvents or surfactants have to be used for dissolution, wasting reagents and increasing costs. These problems affect the further research and application of tetrabromophenol blue.

[0005] Therefore, how to overcome the deficiencies of the prior art and increase the water solubility of tetrabromophenol blue to achieve the purpose of convenient use is a technical problem that needs to be solved at present. Summary of the Invention

[0006] The purpose of the present invention is to provide a soluble alkali metal salt of tetrabromophenol blue, a preparation method thereof, and an application thereof.

[0007] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0008] The present invention provides an alkali metal salt of tetrabromophenol blue, and the structural formula of the alkali metal salt of tetrabromophenol blue is as follows:

[0009]

[0010] Wherein, M is Li, Na or K;

[0011] The present invention provides a preparation method of an alkali metal salt of tetrabromophenol blue, including the following steps:

[0012] 1) Salt formation: Mix tetrabromophenol blue and an alkali metal salt in a solvent for a salt formation reaction to obtain a crude product of the alkali metal salt of tetrabromophenol blue.

[0013] 2) Recrystallization: Mix the crude product of the alkali metal salt of tetrabromophenol blue with a solvent for recrystallization to obtain the alkali metal salt of tetrabromophenol blue.

[0014] Further, the alkali metal salt is one or more of alkali metal carbonates, alkali metal acetates, and alkali metal bicarbonates.

[0015] Further, in steps 1) and 2), the solvent independently is one or more of tetrahydrofuran, acetone, acetonitrile, dioxane, dimethyl sulfoxide, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether, ethylene glycol dimethyl ether, benzene, toluene, and xylene.

[0016] Further, in step 1), the molar ratio of tetrabromophenol blue to the alkali metal salt is 1:0.8 - 2.0; the mass-to-volume ratio of tetrabromophenol blue to the solvent is 1 g:1 - 20 mL.

[0017] Further, the temperature of the salt formation reaction is 25 - 85 °C, and the time of the salt formation reaction is 0.5 - 24 h.

[0018] Further, in step 2), the mass-to-volume ratio of the crude tetrabromophenol blue alkali metal salt to the solvent is 1 g:1 - 20 mL.

[0019] Further, the temperature of the recrystallization is 30 - 85 °C, and the time of the recrystallization is 0.5 - 24 h.

[0020] The present invention provides an application of a tetrabromophenol blue alkali metal salt in the preparation of an albumin detection reagent.

[0021] The present invention provides an application of a tetrabromophenol blue alkali metal salt as a color fixative.

[0022] Advantages of the present invention:

[0023] By subjecting tetrabromophenol blue to salt formation and recrystallization to obtain a tetrabromophenol blue alkali metal salt, the present invention overcomes the problem of poor water solubility of existing tetrabromophenol blue. The finally obtained tetrabromophenol blue alkali metal salt product has a purity of 99.0% and a total yield of 80%; moreover, the preparation method is simple, the conditions are mild, the product purity is high, the yield is high, the cost is low, and it can be mass-produced, which is beneficial for further applications in diagnostic reagents and hair dyes. Specific embodiments

[0024] The present invention provides a tetrabromophenol blue alkali metal salt, and the structural formula of the tetrabromophenol blue alkali metal salt is as follows:

[0025]

[0026] Among them, M is Li, Na, or K.

[0027] In the present invention, the tetrabromophenol blue alkali metal salt is preferably lithium tetrabromophenol blue or sodium tetrabromophenol blue.

[0028] The present invention provides a method for preparing an alkali metal salt of tetrabromophenol blue, comprising the following steps:

[0029] 1) Salt formation: Mix tetrabromophenol blue and an alkali metal salt in a solvent for a salt formation reaction to obtain a crude product of the alkali metal salt of tetrabromophenol blue;

[0030] 2) Recrystallization: Mix the crude product of the alkali metal salt of tetrabromophenol blue with a solvent for recrystallization to obtain the alkali metal salt of tetrabromophenol blue.

[0031] In the present invention, in steps 1) and 2), the solvent is independently one or more of tetrahydrofuran, acetone, acetonitrile, dioxane, dimethyl sulfoxide, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether, ethylene glycol dimethyl ether, benzene, toluene, and xylene, preferably one or more of tetrahydrofuran, acetone, acetonitrile, and dioxane.

[0032] In the present invention, the alkali metal salt is one or more of an alkali metal carbonate, an alkali metal acetate, and an alkali metal bicarbonate, preferably an alkali metal bicarbonate, and more preferably lithium bicarbonate, sodium bicarbonate, or potassium bicarbonate.

[0033] In step 1) of the present invention, the molar ratio of tetrabromophenol blue to the alkali metal salt is 1:0.8 - 2.0, preferably 1:0.9 - 1.8, and more preferably 1:1 - 1.6.

[0034] In step 1) of the present invention, the mass-volume ratio of tetrabromophenol blue to the solvent is 1 g:1 - 20 mL, preferably 1 g:2 - 18 mL, and more preferably 1 g:2 - 16 mL.

[0035] In step 1) of the present invention, the temperature of the salt formation reaction is 25 - 85 °C, and the time of the salt formation reaction is 0.5 - 24 h; preferably, the temperature of the salt formation reaction is 30 - 80 °C, and the time of the salt formation reaction is 0.5 - 13 h; more preferably, the temperature of the salt formation reaction is 35 - 75 °C, and the time of the salt formation reaction is 1 - 12 h.

[0036] In step 2) of the present invention, the recrystallization is carried out by recrystallizing once with each of two different aprotic solvents;

[0037] In step 2) of the present invention, when the first recrystallization solvent is ethyl acetate, the second recrystallization solvent is preferably one or more of ether, isobutyl ether, and isopropyl ether.

[0038] In step 2) of the present invention, when the first recrystallization solvent is dichloromethane, the second recrystallization solvent is preferably one or more of tetrahydrofuran, isopropyl ether, acetone, acetonitrile, and dioxane.

[0039] In step 2) of the present invention, when the first recrystallization solvent is chloroform, the second recrystallization solvent is preferably one or more of isobutyl ether, isopropyl ether, benzene, toluene, and xylene.

[0040] In step 2) of the present invention, the mass-to-volume ratio of the crude product of the alkali metal salt of tetrabromophenol blue to the solvent is 1 g: 1-20 mL, preferably 1 g: 2-18 mL, and more preferably 1 g: 2-16 mL.

[0041] In step 2) of the present invention, the temperature of the recrystallization is 30-85 °C, and the time of the recrystallization is 0.5-24 h; preferably, the temperature of the recrystallization is 35-80 °C, and the time of the recrystallization is 0.5-13 h. More preferably, the temperature of the recrystallization is 40-75 °C, and the time of the recrystallization is 1-12 h.

[0042] In the present invention, when the solvent used is a proton solvent, it will cause the color of the alkali metal salt of tetrabromophenol blue to deepen and is not suitable for use; the selected solvent is a non-proton solvent, and the color of the alkali metal salt of tetrabromophenol blue does not change and can be used.

[0043] In step 1) of the present invention, when the mass-to-volume ratio of the crude product of the alkali metal salt of tetrabromophenol blue to the solvent is too large, the recrystallization is not sufficient and the purification effect is not good; when the mass-to-volume ratio of the crude product of the alkali metal salt of tetrabromophenol blue to the solvent is too small, the reagent is wasted and the yield is reduced.

[0044] In step 2) of the present invention, when the temperature of the recrystallization is lower than 35 °C, the dissolution and dispersion are not sufficient; when the temperature of the recrystallization is higher than 80 °C, the color of the product is too deep; when the temperature of the recrystallization is 40-75 °C, the recrystallization is relatively sufficient and the effect is good. When the time of the recrystallization is less than 1 hour, the dissolution and dispersion are not sufficient; when the time of the recrystallization is greater than 12 hours, the color of the product deepens.

[0045] In step 2) of the present invention, in the first recrystallization, the alkali metal salt of tetrabromophenol blue is insoluble in the solvent, while tetrabromophenol is soluble, so that the remaining free tetrabromophenol in the reaction can be removed; in the second solvent recrystallization, the small-polarity small-molecule impurities contained in the alkali metal salt of tetrabromophenol blue are easily soluble in the solvent, while the alkali metal salt of tetrabromophenol blue is insoluble, thereby realizing the removal of impurities; therefore, the recrystallization uses two different non-proton solvents for recrystallization once each, and the effect is good.

[0046] After recrystallization with two non-proton solvents with different properties, the purity of the product of the alkali metal salt of tetrabromophenol blue is as high as 99.0%, and the total yield of the two recrystallizations is as high as 88%.

[0047] In the present invention, the reaction formula for the synthesis of the alkali metal salt of tetrabromophenol blue is as follows:

[0048]

[0049] Among them, M is Li, Na or K.

[0050] The present invention provides an application of a tetrabromophenol blue alkali metal salt in the preparation of an albumin detection reagent.

[0051] The present invention provides an application of a tetrabromophenol blue alkali metal salt as a color fixing agent, preferably as a color fixing agent for hair dyes.

[0052] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0053] The tetrabromophenol blue used in the following experimental examples and embodiments is a commercially available raw material with a purity of 90.23%.

[0054] Experimental Example 1

[0055] Comparison of the effects of salt formation reactions

[0056] (1) Alkali metal salts

[0057] Take the tetrabromophenol blue raw material, weigh 4 portions, each portion being 98.5 grams (0.1 moL), and add them to the reactor respectively. Then, measure 1.1 eq of sodium hydroxide, sodium carbonate, sodium bicarbonate, and sodium acetate respectively, add them to the reactor respectively, add 300 mL of acetonitrile respectively, stir and react at 50 °C for 8 hours, stop the reaction, cool to room temperature, filter, dry the filter cake, weigh, and obtain the crude product. The relevant experimental data are shown in Table 1.

[0058] Table 1 Selection of alkali metal salts

[0059]

[0060] The data in Table 1 show that when sodium hydroxide is used as the reaction base, the alkalinity is too strong, the reaction is relatively fast, but the color of the crude product deepens and is blue-black, which does not meet the requirements; when sodium carbonate is used as the reaction base, the alkalinity is relatively strong and the color of the crude product is green; when sodium acetate is used as the reaction base, the alkalinity is relatively weak, the reaction is relatively slow, and the appearance of the crude product is yellowish-green; compared with sodium hydroxide, when sodium bicarbonate, sodium carbonate or sodium acetate is used as the reactant of the alkali metal salt in the salt formation step, the crude product yield is higher, the purity is higher, and the color is lighter. Thus, it can be seen that specific alkali metal salts are required to achieve the technical purpose of this application.

[0061] (2) Alkali metal salt feeding equivalent

[0062] Take the raw material of tetrabromophenol blue, weigh 5 portions, each portion being 98.5 grams (0.1 moL), and add them to the reactor respectively. Then measure 0.8 eq, 0.9 eq, 1.6 eq, 1.8 eq and 2.0 eq of sodium bicarbonate respectively and add them to the reactor. Add 300 mL of dioxane respectively, stir and react at 60 °C for 3 hours, stop the reaction, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the crude product. The relevant experimental data are shown in Table 2.

[0063] Table 2 Selection of the feeding equivalent of alkali metal salts

[0064]

[0065]

[0066] The data in Table 2 show that: when the feeding ratio of sodium bicarbonate to tetrabromophenol blue is 0.8 eq, the reaction is incomplete; when the feeding ratio is 2.0 eq, the alkali is in excessive amount too much, the color of the crude product deepens, and the excessive alkali is not easy to remove; when the feeding ratio is 0.9 eq - 1.8 eq, the yield is relatively high, the purity is relatively high, and the color is relatively light.

[0067] (3) Salt-forming solvent

[0068] Take the raw material of tetrabromophenol blue, weigh 5 portions, each portion being 98.5 grams (0.1 moL), and add them to the reactor respectively. Then measure 1.15 eq of sodium bicarbonate respectively and add them to the reactor in sequence. Add 300 mL of tetrahydrofuran, acetone, acetonitrile, dioxane, methanol respectively, react at 45 °C for 8 hours, filter after the reaction is completed, dry the filter cake, weigh it, and obtain the crude product. The relevant experimental data are shown in Table 3.

[0069] Table 3 Selection of salt-forming solvents

[0070]

[0071] The data in Table 3 show that: when the reaction solvent is tetrahydrofuran, acetone, acetonitrile or dioxane, the yield can reach over 93% and the purity is over 94%; when the reaction solvent is methanol (protic solvent), the relative yield is lower and the purity is lower.

[0072] (4) Dosage of salt-forming solvent

[0073] Take the raw material of tetrabromophenol blue, weigh 5 portions, each portion being 98.5 grams (0.1 moL), and add them to the reactor respectively. Then measure 1.2 eq of sodium bicarbonate respectively and add them to the reactor. Add acetonitrile according to the mass-volume ratio of 1:1, 1:2, 1:6, 1:18, 1:20 respectively, stir and react at 50 °C for 5 hours, stop the reaction, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the crude product. The relevant experimental data are shown in Table 4.

[0074] Selection of the amount of salifying solvent used in Table 4

[0075]

[0076] The data in Table 4 show that when the mass-volume ratio of tetrabromophenol blue to acetonitrile is 1 g:1 mL, the reaction is incomplete and the purity is low; when the mass-volume ratio is 1 g:20 mL, the yield is too low; when the mass-volume ratio is 1 g:2 - 18 mL, the crude product yield is higher, the purity is higher, and the effect is better.

[0077] (5) Salifying temperature

[0078] Take the tetrabromophenol blue raw material, weigh 5 portions, each portion being 98.5 grams (0.1 moL), and add them to the reactor respectively. Measure 1.3 eq of sodium bicarbonate respectively and add them to the reactor in sequence. Add them to 500 mL of acetonitrile respectively, and stir and react at 30 °C, 35 °C, 50 °C, 75 °C, and 80 °C for 6 hours. Stop the reaction, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the crude product. The relevant experimental data are shown in Table 5.

[0079] Table 5 Selection of salifying temperature

[0080]

[0081]

[0082] The data in Table 5 show that when the reaction temperature is 30 °C, the obtained crude product is orange, the reaction is incomplete, the yield is low, and the purity is low; when the reaction temperature is 80 °C, the obtained crude product is dark green, side reactions increase, the yield is low, and the purity is low; when the reaction temperature is 35 °C - 75 °C, the obtained crude product has a lighter color, a high yield, and a high purity.

[0083] (6) Salifying reaction time

[0084] Take the tetrabromophenol blue raw material, weigh 5 portions, each portion being 98.5 grams (0.1 moL), and add them to the reactor respectively. Measure 1.3 eq of sodium bicarbonate respectively and add them to the reactor. Add them to 500 mL of dioxane respectively, and stir and react at 50 °C for 0.5 hour, 1 hour, 6 hours, 12 hours, and 13 hours. Stop the reaction, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the crude product. The relevant experimental data are shown in Table 6.

[0085] Table 6 Selection of salifying reaction time

[0086]

[0087] The data in Table 6 show that: when the reaction time is 0.5 hour, the color of the crude product is orange, the reaction is not complete enough, the yield is low, the purity is low, and the reaction effect is not good; when the reaction time is 13 hours, the crude product is dark green, side reactions increase, the yield is low, and the purity is low; when the reaction time is 1 - 12 hours, the color of the crude product is lighter, the yield is high, and the purity is high.

[0088] Experimental Example 2

[0089] Comparison of recrystallization effects

[0090] Salt formation reaction: Take 2956.6 g (3.0 moL) of tetrabromophenol blue raw material, add it to the reactor, add 302.4 g of sodium bicarbonate at 1.2 eq, add 9.0 L of acetonitrile, stir and react at 55 °C for 4 hours, stop stirring, cool to room temperature, filter, dry the filter cake, collect, and obtain 2847.3 g of crude tetrabromophenol blue sodium salt, with a yield of 94.2% and a purity of 95.23%, for use in the next experiment;

[0091] (1) First recrystallization solvent

[0092] Take 5 portions of the crude tetrabromophenol blue sodium salt prepared in the previous step, 100 g each, add them to the reactor, add 400 mL of ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, and methanol respectively, stir at 50 °C for 3 hours, stop stirring, cool to room temperature, filter, dry the filter cake, weigh, and obtain pure products. The relevant experimental data are shown in Table 7.

[0093] Table 7 Selection of the first recrystallization solvent

[0094]

[0095] The data in Table 7 show that: when the first recrystallization solvents are ethyl acetate, dichloromethane, and chloroform, the yields are relatively high and the purities are relatively high; when the recrystallization solvent is carbon tetrachloride, the yield is lower and the purity is lower; when the recrystallization solvent is methanol, both the product yield and purity are lower than those of carbon tetrachloride.

[0096] (2) Second recrystallization solvent

[0097] First recrystallization: Take 500.0 g of the crude tetrabromophenol blue sodium salt prepared in the previous step, add it to the reactor, add 2000 mL of ethyl acetate, stir at 50 °C for 3 hours, stop stirring, cool to room temperature, filter, dry the filter cake, weigh, and obtain 476.0 g of pure product, with a yield of 95.2% and a purity of 97.88%;

[0098] Second recrystallization: Take the first recrystallization product obtained in the previous step, weigh 5 portions, each portion being 100 grams, add them to the reactor respectively, and then add 500 mL of ether, isopropyl ether, isobutyl ether, n-propyl ether, and ethanol respectively. Stir at 35 °C for 10 hours, stop stirring, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the pure product. The relevant experimental data are shown in Table 8.

[0099] Table 8 Selection of solvents for the second recrystallization

[0100]

[0101] The data in Table 8 show that when the recrystallization solvents are ether, isobutyl ether, and isopropyl ether, the purity of the pure products obtained after the second recrystallization all reaches over 99%, and the yields of the second recrystallization are all above 94%; when the recrystallization solvent is n-propyl ether, the purity of the obtained pure product is relatively low and the yield is relatively low, while when the recrystallization solvent is ethanol, both the purity and yield of the obtained product are lower than those of n-propyl ether.

[0102] (3) Usage amount of recrystallization solvent

[0103] Take the crude product of sodium tetrabromophenolphthalein obtained in the previous step, weigh 5 portions, each portion being 100 grams, add them to the reactor respectively, and then add ethyl acetate according to the mass-volume ratio of g:mL of 1:1, 1:2, 1:6, 1:18, and 1:20 respectively. Stir at 60 °C for 2 hours, stop stirring, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the product. The relevant experimental data are shown in Table 9.

[0104] Table 9 Selection of the usage amount of recrystallization solvent

[0105]

[0106]

[0107] The data in Table 9 show that when the mass-volume ratio of the crude sodium tetrabromophenolphthalein to ethyl acetate is 1 g:1 mL, the stirring and dispersion are not sufficient enough, the recrystallization is incomplete, and the purity of the product is relatively low; when the mass-volume ratio is 1 g:20 mL, the yield of the product is too low; when the mass-volume ratio is 1 g:2 - 18 mL, the yield is relatively high and the purity is relatively high.

[0108] (4) Recrystallization temperature

[0109] Take the crude product of sodium tetrabromophenolphthalein obtained in the previous step, weigh 5 portions, each portion being 100 grams, add them to the reactor respectively, add 500 mL of chloroform respectively, and stir at 35 °C, 40 °C, 55 °C, 75 °C, and 80 °C for 4 hours respectively. Stop stirring, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the product. The relevant experimental data are shown in Table 10.

[0110] Table 10 Selection of recrystallization temperature

[0111]

[0112] Table 10 data shows that: the recrystallization temperature is 35 °C, the recrystallization is not sufficient, the purity is low and there is no improvement; the reaction temperature is 80 °C, the obtained crude product is dark green, side reactions increase, the purity does not increase but decreases; the reaction temperature is 40 - 75 °C, the color of the product does not deepen, the yield is high and the purity is high.

[0113] (5) Recrystallization time

[0114] Take 5 portions of the crude sodium salt of tetrabromophenol blue prepared in the previous step, each portion weighing 100 g, and add them to the reactor in sequence. Then add ethyl acetate according to the mass - volume ratio of 1 g:2 mL, and stir for 0.5 hour, 1 hour, 6 hours, 12 hours, and 13 hours respectively. Stop stirring, cool to room temperature, filter, dry the filter cake, weigh it, and obtain the product. The relevant experimental data are shown in Table 11.

[0115] Table 11 Selection of recrystallization time

[0116]

[0117] Table 11 data shows that: the recrystallization time is 0.5 hour, the recrystallization is not sufficient and the purity does not increase significantly; the recrystallization time is 13 hours, the color of the obtained crude product deepens, side reactions increase and the purity decreases; the recrystallization time is 1 - 12 hours, the color of the product remains unchanged, the yield is high and the purity is high.

[0118] Example 1

[0119] 1) Salt formation: Weigh 98.5 g (0.1 moL) of tetrabromophenol blue and add it to the reactor. Add 1.4 eq of lithium bicarbonate, add 400 mL of acetone, stir and react at 40 °C for 6 hours. Stop stirring, cool to room temperature, filter, dry the filter cake, collect it, and obtain 92.5 g of the crude lithium salt of tetrabromophenol blue, with a yield of 93.3% and a purity of 95.43%;

[0120] 2) Recrystallization:

[0121] First recrystallization: Add 92.5 g of the crude lithium salt of tetrabromophenol blue obtained in the previous step to the reactor, add 300 mL of chloroform, stir at 55 °C for 2 hours. Stop stirring, cool to room temperature, filter, dry the filter cake, collect it, weigh 87.4 g, with a yield of 94.5% and a purity of 97.51%;

[0122] Second recrystallization: 87.4 g of the product obtained in the previous step was added to the reactor, 300 mL of isopropyl ether was added, and the mixture was stirred at 55 °C for 1 hour. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried, collected to obtain pure lithium salt of tetrabromophenol blue, weighing 83.2 g, with a yield of 95.2% and an overall yield of 83.9% and a purity of 99.66%.

[0123] Example 2

[0124] 1) Salt formation: 98.5 g (0.1 moL) of tetrabromophenol blue was weighed and added to the reactor, 1.3 eq of sodium bicarbonate was added, 300 mL of acetonitrile was added, and the mixture was stirred at 55 °C for 4 hours. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried, collected to obtain 92.5 g of the crude product, with a yield of 92.4% and a purity of 95.58%;

[0125] 2) Recrystallization:

[0126] First recrystallization: 92.5 g of the crude sodium salt of tetrabromophenol blue obtained in the previous step was all added to the reactor, 200 mL of ethyl acetate was added, and the mixture was stirred at 50 °C for 2 hours. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried, collected, weighing 90.0 g, with a yield of 95.1% and a purity of 97.34%;

[0127] Second recrystallization: 90.0 g of the product obtained in the previous step was added to the reactor, 200 mL of isopropyl ether was added, and the mixture was stirred at 50 °C for 1 hour. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried, collected to obtain pure sodium salt of tetrabromophenol blue, weighing 84.3 g, with a yield of 93.7% and an overall yield of 83.7% and a purity of 99.64%.

[0128] Example 3

[0129] 1) Salt formation: 98.5 g (0.1 moL) of tetrabromophenol blue was weighed and added to the reactor, 1.2 eq of potassium bicarbonate was added, 300 mL of dioxane was added, and the mixture was stirred at 50 °C for 3 hours. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried, collected to obtain 93.3 g of the crude product, with a yield of 91.1% and a purity of 95.14%;

[0130] 2) Recrystallization:

[0131] First recrystallization: 93.3 g of the crude potassium salt of tetrabromophenol blue obtained in the previous step was added to the reactor, 200 mL of dichloromethane was added, and the mixture was stirred at 40 °C for 2 hours. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried, collected, weighing 88.4 g, with a yield of 94.7% and a purity of 97.51%;

[0132] Second recrystallization: 88.4 g of the product obtained in the previous step was added to a reactor, 200 mL of isopropyl ether was added, and the mixture was stirred at 40 °C for 1 hour. Stirring was stopped, and the mixture was cooled to room temperature, filtered, and the filter cake was dried and collected to obtain pure potassium tetrabromophenol blue, weighing 84.1 g, with a yield of 95.1%, an overall yield of 82.2%, and a purity of 99.27%.

[0133] Test example

[0134] The solubility data of lithium tetrabromophenol blue, sodium tetrabromophenol blue, potassium tetrabromophenol blue and tetrabromophenol blue obtained in Test Examples 1 to 3 are compared in Table 12.

[0135] Table 12 Solubility of alkali metal salts of tetrabromophenol blue obtained in Examples 1 to 3

[0136] Solvent Tetrabromophenol Blue Lithium Tetrabromophenol Blue Sodium Tetrabromophenol Blue Potassium Tetrabromophenol Blue Water Sparingly soluble Dissolve Dissolve Dissolve Methanol Slightly soluble Sparingly soluble Sparingly soluble Sparingly soluble Ethanol Slightly soluble Insoluble Insoluble Insoluble Tetrahydrofuran Dissolve Insoluble Insoluble Insoluble

[0137] Definition of the name terms expressed by solubility:

[0138] Very soluble: It means that 1 g (mL) of solute can dissolve in less than 1 mL of solvent;

[0139] Freely soluble: It means that 1 g (mL) of solute can dissolve in 1 to less than 10 mL of solvent;

[0140] Soluble: It means that 1 g (mL) of solute can dissolve in 10 to less than 30 mL of solvent;

[0141] Sparingly soluble: It means that 1 g (mL) of solute can dissolve in 30 to less than 100 mL of solvent;

[0142] Slightly soluble: It means that 1 g (mL) of solute can dissolve in 100 to less than 1000 mL of solvent;

[0143] Very slightly soluble: It means that 1 g (mL) of solute can dissolve in 1000 to less than 10000 mL of solvent;

[0144] Practically insoluble or insoluble: It means that 1 g (mL) of solute cannot completely dissolve in 10000 mL of solvent;

[0145] As can be seen from Table 12, the solubility of lithium tetrabromophenol blue, sodium tetrabromophenol blue and potassium tetrabromophenol blue in water increases significantly.

[0146] Example 4

[0147] Application of lithium tetrabromophenol blue in detection reagents

[0148] 1) Preparation of solutions: Preparation of chromogenic solution: Weigh 0.4 g of lithium salt of tetrabromophenol blue and 0.5 g of sodium dodecyl sulfonate respectively, dissolve them in 100 mL of distilled water, stir evenly and set aside; Preparation of albumin standard solution: Weigh human serum albumin, dissolve it with distilled water, and prepare concentration gradients of 0.1, 0.2, 0.4, 0.8, 1.6, and 3.2 g / L respectively, and set aside; Preparation of buffer solution: Prepare 100 mL of citric acid - sodium citrate buffer solution with pH 3.0, stir evenly and set aside;

[0149] 2) Determination of albumin content: In 7 colorimetric tubes, add 4.8 mL of citric acid - sodium citrate buffer solution respectively, add 100 μL of chromogenic solution, add 100 μL of 6 kinds of concentration gradients of human serum albumin standard solution respectively, add 100 μL of the protein standard solution to be measured, establish a standard curve, and directly measure the albumin content in the sample to be measured.

[0150] Example 5

[0151] Application of sodium salt of tetrabromophenol blue in detection reagent

[0152] 1) Preparation of solutions: Preparation of chromogenic solution: Weigh 0.35 g of sodium salt of tetrabromophenol blue and 0.5 g of sodium dodecyl sulfonate respectively, dissolve them in 100 mL of distilled water, stir evenly and set aside; Preparation of albumin standard solution: Weigh human serum albumin, dissolve it with distilled water, and prepare concentration gradients of 0.1, 0.2, 0.4, 0.8, 1.6, and 3.2 g / L respectively, and set aside; Preparation of buffer solution: Prepare 100 mL of citric acid - sodium citrate buffer solution with pH 3.0, stir evenly and set aside;

[0153] Determination of albumin content: In 7 colorimetric tubes, add 4.8 mL of citric acid - sodium citrate buffer solution respectively, add 100 μL of chromogenic solution, add 100 μL of 6 kinds of concentration gradients of human serum albumin standard solution respectively, add 100 μL of the protein standard solution to be measured, establish a standard curve, and directly measure the albumin content in the sample to be measured.

[0154] Example 6

[0155] Application of potassium salt of tetrabromophenol blue in detection reagent

[0156] 1) Preparation of solutions: Preparation of chromogenic solution: Weigh 0.33 g of potassium salt of tetrabromophenol blue and 0.5 g of sodium dodecyl sulfonate respectively, dissolve them in 100 mL of distilled water, stir evenly and set aside; Preparation of albumin standard solution: Weigh human serum albumin, dissolve it with distilled water, and prepare concentration gradients of 0.1, 0.2, 0.4, 0.8, 1.6, and 3.2 g / L respectively, and set aside; Preparation of buffer solution: Prepare 100 mL of citric acid - sodium citrate buffer solution with pH 3.0, stir evenly and set aside;

[0157] 2) Determination of albumin content: In 7 colorimetric tubes, add 4.8 mL of citric acid - sodium citrate buffer solution, add 100 μL of chromogenic solution, add 100 μL of human serum albumin standard solution of 6 concentrations respectively, add 100 μL of the protein sample to be measured, establish a standard curve, and directly measure the albumin content in the sample to be measured.

[0158] Example 7

[0159] Application of lithium salt of tetrabromophenol blue in hair dye

[0160] The components of the hair dye include: lithium salt of tetrabromophenol blue, 1,8 - dihydroxynaphthalene, mushroom tyrosinase, pH regulator, tannic acid, excipient, etc. Among them, the pH regulator is sodium dihydrogen phosphate - dipotassium hydrogen phosphate buffer solution, and the excipient includes one or more combinations of hydroxyethyl cellulose, sodium dodecylbenzenesulfonate, glycerol, xanthan gum, etc.

[0161] The first component of the hair dye: 1,8 - dihydroxynaphthalene: 0.03%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzenesulfonate: 1.5%, glycerol: 5%, pH 3.0 phosphate buffer solution and the balance of water, and the sum of the mass percentages of each component is 100%.

[0162] The second component: mushroom tyrosinase: 0.03%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzenesulfonate: 1.5%, glycerol: 5%, pH 3.0 phosphate buffer solution and the balance of water, and the sum of the mass percentages of each component is 100%.

[0163] The third component: lithium salt of tetrabromophenol blue: 5%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzenesulfonate: 1.5%, glycerol: 5%, pH 3.0 phosphate buffer solution and the balance of water, and the sum of the mass percentages of each component is 100%.

[0164] The fourth component: tannic acid: 4%, xanthan gum: 8%, pH 3.0 phosphate buffer solution and the balance of water, and the sum of the mass percentages of each component is 100%.

[0165] Wash the white hair, mix the first, second and third components in a mass ratio of (1:1:1) and apply them to the hair, wrap the hair for 30 min, then wash the hair, apply the fourth component with a mass ratio of 1:1 to the first component to the hair, wrap the hair for 30 min, and wash the hair. The result is that the hair color is yellow - green.

[0166] Example 8

[0167] Application of sodium salt of tetrabromophenol blue in hair dye

[0168] The components of the hair dye include: sodium tetrabromophenol blue, 1,8-dihydroxynaphthalene, mushroom tyrosinase, pH regulator, tannic acid, excipient, etc. Among them, the pH regulator is a sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, and the excipient includes one or more combinations of hydroxyethyl cellulose, sodium dodecylbenzene sulfonate, glycerol, xanthan gum, etc.

[0169] The first component of the hair dye is: 1,8-dihydroxynaphthalene: 0.03%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzene sulfonate: 1.5%, glycerol: 5%, pH 6.0 phosphate buffer solution and the balance is water, and the sum of the mass percentages of each component is 100%.

[0170] The second component is: mushroom tyrosinase: 0.03%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzene sulfonate: 1.5%, glycerol: 5%, pH 6.0 phosphate buffer solution and the balance is water, and the sum of the mass percentages of each component is 100%.

[0171] The third component is: sodium tetrabromophenol blue: 5%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzene sulfonate: 1.5%, glycerol: 5%, pH 6.0 phosphate buffer solution and the balance is water, and the sum of the mass percentages of each component is 100%.

[0172] The fourth component is: tannic acid: 4%, xanthan gum: 8%, pH 6.0 phosphate buffer solution and the balance is water, and the sum of the mass percentages of each component is 100%.

[0173] Wash the white hair, mix the first, second and third components in a mass ratio of (1:1:1) and apply them to the hair, wrap the hair for 30 minutes, then wash the hair, apply the fourth component with a mass ratio of 1:1 to the first component to the hair, wrap the hair for 30 minutes, and wash the hair. As a result, the hair color is blue-green.

[0174] Example 9

[0175] Application of potassium tetrabromophenol blue in hair dye

[0176] The components of the hair dye include: potassium tetrabromophenol blue, 1,8-dihydroxynaphthalene, mushroom tyrosinase, pH regulator, tannic acid, excipient, etc. Among them, the pH regulator is a sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, and the excipient includes one or more combinations of hydroxyethyl cellulose, sodium dodecylbenzene sulfonate, glycerol, xanthan gum, etc.

[0177] The first component of the hair dye is: 1,8-dihydroxynaphthalene: 0.03%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzene sulfonate: 1.5%, glycerol: 5%, pH 8.0 phosphate buffer solution and the balance is water, and the sum of the mass percentages of each component is 100%.

[0178] The second component group is: mushroom tyrosinase: 0.03%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzenesulfonate: 1.5%, glycerol: 5%, pH 8.0 phosphate buffer and the balance is water, and the sum of the mass percentages of each component is 100%.

[0179] The third component group is: potassium tetrabromophenol blue: 5%, hydroxyethyl cellulose: 1.5%, sodium dodecylbenzenesulfonate: 1.5%, glycerol: 5%, pH 8.0 phosphate buffer and the balance is water, and the sum of the mass percentages of each component is 100%.

[0180] The fourth component group is: tannic acid: 4%, xanthan gum: 8%, pH 8.0 phosphate buffer and the balance is water, and the sum of the mass percentages of each component is 100%.

[0181] Wash the white hair, mix the first component, the second component and the third component in a mass ratio of (1:1:1) and apply it to the hair, wrap the hair for 30 minutes, then wash the hair, apply the fourth component with a mass ratio of 1:1 to the first component to the hair, and wrap the hair for 30 minutes, and then wash the hair. As a result, the hair color is blue-black.

[0182] As can be seen from the above examples, the present invention provides a tetrabromophenol blue alkali metal salt, its preparation method and application. The present invention obtains the tetrabromophenol blue alkali metal salt by salifying and recrystallizing tetrabromophenol blue, overcomes the problem of poor water solubility of existing tetrabromophenol blue. Finally, the purity of the obtained tetrabromophenol blue alkali metal salt product reaches 99.0%, and the total yield reaches 80%; and the preparation process method is simple, the conditions are mild, the product purity is high, the yield is high, the cost is low, and it can be mass-produced, which is beneficial to further application in albumin detection reagents and hair dyes.

[0183] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can still be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A preparation method of an alkali metal salt of tetrabromophenol blue, characterized in that, It includes the following steps: 1) Salt formation: Tetrabromophenol blue and an alkali metal salt are mixed in a solvent for a salt formation reaction to obtain a crude product of the alkali metal salt of tetrabromophenol blue; 2) Recrystallization: The crude product of the alkali metal salt of tetrabromophenol blue is mixed with a solvent for recrystallization to obtain the alkali metal salt of tetrabromophenol blue; The structural formula of the alkali metal salt of tetrabromophenol blue is as follows: ； wherein M is Li, Na or K; The alkali metal salt is sodium bicarbonate, potassium bicarbonate or lithium bicarbonate; In step 1), the solvent is tetrahydrofuran, acetone, acetonitrile or dioxane; In step 2), the recrystallization is carried out by recrystallizing once with each of two different aprotic solvents; When the first recrystallization solvent is ethyl acetate, the second recrystallization solvent is diethyl ether, isobutyl ether or isopropyl ether; When the first recrystallization solvent is dichloromethane, the second recrystallization solvent is isopropyl ether; When the first recrystallization solvent is chloroform, the second recrystallization solvent is isopropyl ether; In step 1), the molar ratio of tetrabromophenol blue to the alkali metal salt is 1:0.9 - 1.8; the mass-volume ratio of tetrabromophenol blue to the solvent is 1 g: 2 - 18 mL; The temperature of the salt formation reaction is 35 - 75 °C, and the time of the salt formation reaction is 1 - 12 h; In step 2), the mass-volume ratio of the crude product of the alkali metal salt of tetrabromophenol blue to the solvent is 1 g: 2 - 18 mL; The temperature of the recrystallization is 40 - 75 °C, and the time of the recrystallization is 1 - 12 h.

Images