Method for recrystallizing and purifying sodium tetraphenylborate

Abstract

The invention provides a method for recrystallizing and purifying sodium tetraphenylborate. The method for recrystallizing and purifying sodium tetraphenylborate comprises the following steps: adding a sodium tetraphenylborate crude product into ethyl acetate, stirring and dissolving, slowly dropwise adding methylbenzene, recrystallizing, filtering, washing and drying to obtain sodium tetraphenylborate with the purity of more than 99%. According to the method, low-toxicity ethyl acetate and methylbenzene are adopted for synergic crystallization, and the target product is selectively separated out by utilizing the difference of the solubility of ethyl acetate and methylbenzene to impurities, so that the hydrolysis and side reaction of sodium tetraphenylborate can be effectively inhibited, trace triphenylboron and other organic impurities are retained in the mother liquor, and the preparation of high-purity sodium tetraphenylborate can be realized; the method has the advantages that the purity is high, the defect of insufficient traditional water phase crystallization purity is overcome, the supersaturation degree is accurately controlled by dropwise adding methylbenzene in a gradient manner, crystal defects and impurity embedding are reduced, and the obtained sodium tetraphenylborate product is high in flowability, has the water content of less than 0.1% and meets the quantitative analysis standard of drugs.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical reagents, in particular to a method for purifying sodium tetraphenylborate by recrystallization. BACKGROUND

[0002] Sodium tetraphenylborate is an important organic metal salt reagent, which plays an irreplaceable role in the fields of analytical chemistry, organic synthesis and pharmaceutical chemistry. Its high purity form is the key prerequisite for ensuring the quantitative precipitation of potassium ions, the preparation of phase transfer catalysts and the purification effect of some active ingredients. However, the existing purification process of sodium tetraphenylborate faces multiple challenges, which seriously restricts its industrial application and the stability of high-end reagents.

[0003] The existing recrystallization method mainly has the problems of insufficient control of crystallization kinetics, direct mixing of poor solvents in the rapid crystallization process, resulting in an increase in crystal defects and embedding of mother liquor impurities, and the conventional gradient cooling method is time-consuming and low in production efficiency. In addition, trace amounts of organic impurities such as triphenylboron in the crude product are difficult to separate effectively by simple recrystallization due to their close solubility with the target product.

[0004] Therefore, it is a technical problem to be solved in the field to develop a recrystallization process with high crystallization efficiency and stable high-purity sodium tetraphenylborate. SUMMARY

[0005] (I) Technical problems solved

[0006] In view of the deficiencies of the prior art, the present application provides a method for purifying sodium tetraphenylborate by recrystallization, which solves the problems raised in the above background technology by combining binary solvent combination with precise recrystallization condition control.

[0007] (II) Technical solutions

[0008] To achieve the above purposes, the present application is implemented by the following technical solutions:

[0009] According to the first aspect of the present application, a method for purifying sodium tetraphenylborate by recrystallization is provided, which comprises the following steps: adding sodium tetraphenylborate crude product into ethyl acetate, stirring and dissolving, slowly adding toluene, recrystallizing, filtering, rinsing and drying to obtain sodium tetraphenylborate with a purity of > 99%.

[0010] Preferably, the recrystallization conditions are as follows: slowly heating to 40-45℃ under stirring, continuously stirring for 1-2h, and then precipitating solids.

[0011] Further preferably, the recrystallization temperature is 40-42℃.

[0012] Preferably, the mass / volume ratio of the sodium tetraphenylborate crude product to ethyl acetate is 1g: 1-3mL.

[0013] The mass of the sodium tetraphenylborate crude product to the volume of toluene is 1g: 1-3mL;

[0014] The volume ratio of ethyl acetate to toluene is 1:1-1.5.

[0015] Preferably, the temperature of the stirring dissolution is -5-0℃, and the stirring dissolution time is 1-2h.

[0016] Preferably, the preparation method of the sodium tetraphenylborate crude product is: reacting chlorobenzene with magnesium to obtain a Grignard reagent, and then adding trimethyl borate and sodium carbonate to the Grignard reagent to obtain the sodium tetraphenylborate crude product.

[0017] Preferably, the molar ratio of the magnesium particles to chlorobenzene is 1:0.76-1.

[0018] The molar ratio of chlorobenzene to trimethyl borate is 1:10-15.

[0019] The volume of chlorobenzene to the mass of sodium carbonate is 1mL: 80-120g.

[0020] Preferably, the Grignard reagent contains iodine ions.

[0021] Beneficial effects

[0022] The application provides a method for recrystallizing and purifying sodium tetraphenylborate.

[0023] (1) The method for recrystallizing and purifying sodium tetraphenylborate provided by the scheme uses low-toxicity ethyl acetate and toluene to cooperatively crystallize, uses the difference in solubility of ethyl acetate and toluene for impurities to selectively precipitate the target product, can effectively inhibit the hydrolysis and side reactions of sodium tetraphenylborate and retain trace amounts of organic impurities such as triphenylboron in the mother liquor, can realize the preparation of high-purity sodium tetraphenylborate, and overcomes the insufficient purity of traditional water-phase crystallization.

[0024] (2) The method for recrystallizing and purifying sodium tetraphenylborate provided by the scheme precisely controls the supersaturation by gradiently adding toluene, reduces the crystal defects and impurity embedding, and the obtained sodium tetraphenylborate product has high fluidity and a water content of <0.1%, satisfying the drug quantitative analysis standard.

[0025] (3) The method for recrystallizing and purifying sodium tetraphenylborate provided by the scheme has the characteristics of low volatility and easy recovery of the solvent system, can greatly reduce the risk of combustion and explosion and the cost of waste liquid treatment, and provides an effective scheme for industrialized production of high-purity sodium tetraphenylborate. DETAILED DESCRIPTION

[0026] For the purposes of promoting an understanding of the principles of the application, the application will now be described more thoroughly. It will be understood, however, that the application can be carried out in many different forms and should not be considered limited to the embodiments or examples set forth in this disclosure. Rather, these embodiments or examples are provided so that this disclosure will convey the principles and substantive information of the application to those skilled in the art.

[0027] Hereinafter, the method for recrystallizing and purifying sodium tetraphenylborate according to the present application will be described in further detail through specific examples. However, it should be understood by those skilled in the art that the following examples are for the purpose of illustration only and should not be construed as limiting the scope of the present application. In the examples, the conditions not specified are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments not specified by the manufacturer are all conventional products that can be commercially available.

[0028] Example 1

[0029] Preparation of sodium tetraphenylborate crude product: In a 500 mL three-necked flask, 24 g of magnesium pellets and a small amount of iodine ions were added, and a reflux condenser tank equipped with a drying tube was attached. A magnetic stirrer was attached, and 40 mL of chlorobenzene and 200 mL of dry tetrahydrofuran were added to a constant pressure dropping funnel. To the three-necked flask, 2 mL of chlorobenzene and 10 mL of tetrahydrofuran were added, and the reaction was initiated by heating with an electric hair dryer. After the reaction was initiated, the mixed solution containing chlorobenzene and tetrahydrofuran was slowly added dropwise, and the reaction system was maintained in a slight reflux state. After the addition of the tetrahydrofuran solution containing chlorobenzene was completed, reflux was continued for 1 h, and the reaction mixture was cooled to room temperature to obtain Grignard reagent. To the Grignard reagent, 20 mL of trimethyl borate solution having a concentration of 0.1 mol / mL was added dropwise, and then 800 mL of aqueous sodium carbonate solution having a concentration of 0.125 g / mL was added. The mixture was stirred for 1 h, and then filtered. The filter cake was washed with water and dried to obtain white sodium tetraphenylborate crude product.

[0030] Purification of sodium tetraphenylborate crude product: 10 g of sodium tetraphenylborate crude product was added to 10 mL of ethyl acetate, and the mixture was stirred while being cooled to 0°C to dissolve the solid. After the solid was dissolved, 10 mL of toluene was slowly added dropwise while maintaining the temperature at 0°C. After the addition was completed, the mixture was stirred at 0°C for 1 h, and then slowly warmed to 40°C in a water bath to recrystallize. The mixture was further stirred for 1 h, and then filtered. Finally, the filter cake was washed with 2 mL of toluene and dried to obtain 6.3 g of sodium tetraphenylborate having an HPLC purity of 99.5%.

[0031] Example 2

[0032] The sodium tetraphenylborate crude product of this example was prepared in the same manner as in Example 1.

[0033] Purification of crude sodium tetraphenylborate: 10 g of crude sodium tetraphenylborate was added to 10 mL of ethyl acetate, stirred to dissolve the solid completely at 0 °C, 10 mL of toluene was added slowly dropwise after dissolution, the temperature was kept at 0 °C, stirred for 1 h at 0 °C after the addition was completed, recrystallized slowly in a water bath to 41 °C, continue to stir for 1 h, filtered, finally washed with 2 mL of toluene, dried, 6.2 g of sodium tetraphenylborate with HPLC purity of 99.6% was obtained.

[0034] Example 3

[0035] The crude sodium tetraphenylborate of this example was prepared by the same method as in Example 1;

[0036] Purification of crude sodium tetraphenylborate: 10 g of crude sodium tetraphenylborate was added to 10 mL of ethyl acetate, stirred to dissolve the solid completely at 0 °C, 10 mL of toluene was added slowly dropwise after dissolution, the temperature was kept at 0 °C, stirred for 1 h at 0 °C after the addition was completed, recrystallized slowly in a water bath to 42 °C, continue to stir for 1 h, filtered, finally washed with 2 mL of toluene, dried, 6.4 g of sodium tetraphenylborate with HPLC purity of 99.3% was obtained.

[0037] Example 4

[0038] The crude sodium tetraphenylborate of this example was prepared by the same method as in Example 1;

[0039] Purification of crude sodium tetraphenylborate: 10 g of crude sodium tetraphenylborate was added to 10 mL of ethyl acetate, stirred to dissolve the solid completely at 0 °C, 10 mL of toluene was added slowly dropwise after dissolution, the temperature was kept at 0 °C, stirred for 1 h at 0 °C after the addition was completed, recrystallized slowly in a water bath to 45 °C, continue to stir for 1 h, filtered, finally washed with 2 mL of toluene, dried, 6.7 g of sodium tetraphenylborate with HPLC purity of 99.0% was obtained.

[0040] Example 5

[0041] The crude sodium tetraphenylborate of this example was prepared by the same method as in Example 1;

[0042] Purification of crude sodium tetraphenylborate: 10 g of crude sodium tetraphenylborate was added to 20 mL of ethyl acetate, stirred to dissolve the solid completely at 0 °C, 20 mL of toluene was added slowly dropwise after dissolution, the temperature was kept at 0 °C, stirred for 1 h at 0 °C after the addition was completed, recrystallized slowly in a water bath to 40 °C, continue to stir for 1 h, filtered, finally washed with 2 mL of toluene, dried, 6.3 g of sodium tetraphenylborate with HPLC purity of 99.6% was obtained.

[0043] Comparative Example 1

[0044] The crude sodium tetraphenylborate of the present comparative example is prepared in the same way as in Example 1;

[0045] Purification of the crude sodium tetraphenylborate: 10 g of the crude sodium tetraphenylborate is added to 10 mL of ethyl acetate, and the solid is completely dissolved by stirring at 0°C. After dissolution, 10 mL of toluene is slowly added dropwise while maintaining the temperature at 0°C. After the addition is completed, stirring is continued at 0°C for 1 h, and recrystallization is carried out by slowly warming to 50°C in a water bath. Stirring is continued for 1 h, and the mixture solution turns yellow. The crystals are precipitated in the form of oil, and cannot be filtered. Through detection, the HPLC purity is 91.3%, and the benzene boronic acid content is 5.2%.

[0046] Comparative Example 2

[0047] The crude sodium tetraphenylborate of the present comparative example is prepared in the same way as in Example 1;

[0048] Purification of the crude sodium tetraphenylborate: 10 mL of ethyl acetate and 10 mL of toluene are mixed, and 10 g of the crude sodium tetraphenylborate is added to the mixed solution. Recrystallization is carried out by slowly warming to 40°C in a water bath. Stirring is continued for 1 h, and flocculent precipitates appear in the mixed solution, which cannot be filtered. Through detection, the HPLC purity is 97.3%, and the triphenyl boron residue is 0.9%. The mother liquor is severely embedded.

[0049] Comparative Example 3

[0050] The crude sodium tetraphenylborate of the present comparative example is prepared in the same way as in Example 1;

[0051] Purification of the crude sodium tetraphenylborate: 10 g of the crude sodium tetraphenylborate is added to 30 mL of ethyl acetate, and the solid is completely dissolved by stirring at 0°C. After dissolution, 30 mL of toluene is slowly added dropwise while maintaining the temperature at 0°C. After the addition is completed, stirring is continued at 0°C for 1 h, and recrystallization is carried out by slowly warming to 40°C in a water bath. Stirring is continued for 1 h, and the mixture solution turns yellow. The crystals are precipitated in the form of oil, and cannot be filtered. Through detection, the HPLC purity is 97.3%, and the triphenyl boron residue is 0.9%. The mother liquor is severely embedded.

[0052] From the comparison of the above examples and comparative examples, it can be seen that, by first dissolving the sodium tetraphenylborate in ethyl acetate, then combining gradient dropwise addition of toluene, and combining recrystallization at a temperature of 40-45°C, the solvent composition, temperature, and kinetic process can be synergistically controlled, and stable production of high-purity sodium tetraphenylborate can be realized.

[0053] Although embodiments of the present application have been shown and described, it is to be understood that various modifications, substitutions, replacements and changes can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A method for recrystallizing and purifying sodium tetraphenylborate, characterized in that: The crude sodium tetraphenylborate was added to ethyl acetate, stirred and dissolved, and then toluene was slowly added dropwise. The mixture was recrystallized, filtered, rinsed and dried to obtain sodium tetraphenylborate with a purity of >99%.

2. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 1, characterized in that: The recrystallization conditions are as follows: slowly heating to 40-45° C. under stirring, continuously stirring for 1-2 hours, and waiting for solid precipitation.

3. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 2, characterized in that: The recrystallization temperature is 40-42°C.

4. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 1, characterized in that: The mass ratio of the crude sodium tetraphenylborate to the volume ratio of ethyl acetate is 1 g: 1-3 mL; The mass ratio of the crude sodium tetraphenylborate to toluene is 1 g: 1-3 mL; The volume ratio of ethyl acetate to toluene is 1:1 to 1.

5.

5. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 1, characterized in that: The stirring and dissolving temperature is -5 to 0°C, and the stirring and dissolving time is 1 to 2 hours.

6. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 1, characterized in that: The preparation method of the crude sodium tetraphenylborate comprises the following steps: reacting chlorobenzene with metallic magnesium to obtain a Grignard reagent, and then adding trimethyl borate and sodium carbonate to the Grignard reagent to obtain the crude sodium tetraphenylborate.

7. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 6, characterized in that: The molar ratio of the magnesium particles to chlorobenzene is 1:0.76-1; The molar ratio of chlorobenzene to trimethyl borate is 1:10-15; The mass ratio of the volume of chlorobenzene to the sodium carbonate is 1 mL: 80-120 g.

8. A method for recrystallizing and purifying sodium tetraphenylborate according to claim 6, characterized in that: The Grignard reagent contains iodide ions.