Purification method of 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide

Abstract

The invention discloses a purification method of 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, and belongs to the technical field of oxygen-containing acid esters of phosphorus, and the purification method comprises the following steps: dissolving, purifying by an adsorption column, and crystallizing and purifying. The adsorption column purification method comprises the steps of adsorption column preparation, adsorption and elution, and eluent treatment. According to the purification method of the 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, disclosed by the invention, impurities which are similar to those of the 9, 10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide in physical property and are difficult to remove can be removed, the yield is improved, and the obtained product is high in purity; the obtained product is a white crystal in appearance, the yield is 85.7-87.8%, the final purity is 99.81-99.90%, and the melting point range is narrow and is close to a standard melting point.

Description

Technical Field

[0001] The invention belongs to the technical field of phosphorus oxygen-containing acid esters, and specifically relates to a method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. Background Art

[0002] 9,10-Dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) is a multifunctional organophosphorus compound that can be used as an antibacterial agent, antioxidant, anti-fading agent, flame retardant and reactive monomer in polymer synthesis. It is particularly outstanding in the field of flame retardancy: as a new generation of halogen-free, environmentally friendly flame retardant modifier, DOPO achieves high efficiency flame retardancy by inhibiting the combustion chain reaction and promoting the formation of carbon layer. It has been widely used in electronic packaging materials, engineering plastics and textile flame retardant treatment. In the fields of electronic materials, high-performance flame retardants, optoelectronic devices, which have extremely high requirements for the chemical stability and functional reliability of materials, the purity requirements for DOPO are also very high. However, industrial DOPO generally has the disadvantages of excessive impurity content, high chroma and low purity, which limits the application of DOPO.

[0003] The synthesis process of DOPO mainly includes four reaction steps: (1) o-phenylphenol (OPP) and phosphorus trichloride undergo monoesterification to produce o-phenylphenoxyphosphonium dichloride (CC); (2) CC undergoes acylation at high temperature under the catalysis of metal chloride to obtain the intermediate 6-chloro-(6-hydrogen)-dibenzo-(c,e)-oxaphosphorinyl (CDOP); (3) CDOP is hydrolyzed to obtain 2'-hydroxybiphenyl-2-phosphorous acid (HPPA); (4) HPPA is dehydrated and cyclized to obtain DOPO.

[0004] The esterification reaction between OPP and phosphorus trichloride is not completely selective to produce monoester CC, but also produces diesters and triesters. After acylation and hydrolysis, the diesters and triesters will produce OPP, and some OPP will remain in the product DOPO. At the same time, in addition to intramolecular dehydration to produce DOPO, HPPA dehydration cyclization will also cause dehydration between HPPA molecules to produce intermolecular dehydrates. These intermolecular dehydrates also contain benzene rings and phosphorus-oxygen double bonds, and some also contain phosphorus-hydrogen bonds, which are highly similar to the molecular structure of DOPO.

[0005] The existing technology usually uses recrystallization to improve the purity of DOPO, because crude DOPO contains OPP and intermolecular dehydrates, and residual HPPA that has not undergone cyclization. The physical properties of these impurities are similar to those of DOPO, and conventional crystallization methods are difficult to remove.

[0006] CN118239983A discloses a method for preparing and purifying DOPO by low-temperature cyclization reaction. The invention passes the prepared organic liquid containing DOPO through a silica gel column, and the insoluble mechanical impurities in the organic liquid are intercepted by the silica gel layer, while the polar impurities with color are adsorbed to the silica gel layer, completing the impurity removal and decolorization treatment, and then obtaining the finished product by reduced pressure distillation; however, the silica gel column can only remove insoluble impurities and polar impurities, and has limited effect on removing intermolecular dehydrates and HPPA with similar physical properties to DOPO. Summary of the invention

[0007] In view of the shortcomings of the prior art, the present invention provides a method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, which can remove impurities that are similar to DOPO in physical properties and are difficult to remove, improve the yield, and obtain a product with high purity.

[0008] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows: a method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, comprising the following steps: dissolution, adsorption column purification, and crystallization purification.

[0009] The dissolving method comprises dissolving the crude product of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide in toluene, adding activated carbon for decolorization, filtering to remove insoluble impurities and activated carbon, and obtaining a mother liquor; The mass ratio of the crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, toluene and activated carbon is 10:80-100:4-5.

[0010] The adsorption column purification method comprises preparing the adsorption column, adsorption and elution, and eluent treatment; The method for preparing the adsorption column comprises: dispersing activated silica gel in toluene, adding 3-[(2,3)-epoxypropyloxy]propylmethyldimethoxysilane and triethylamine, heating to 90-100° C. in a nitrogen atmosphere, stirring for reaction for 4-6 hours, filtering after the reaction is completed, washing with toluene, and drying to obtain modified silica gel; dissolving cyclodextrin in dimethyl sulfoxide, adding sodium hydroxide until the pH value is 13-14, mixing evenly and standing for 4-6 hours to obtain a cyclodextrin solution, dispersing the modified silica gel in dimethyl sulfoxide to obtain a modified silica gel dispersion, adding the cyclodextrin solution to the modified silica gel dispersion, heating to 100-110° C., stirring for reaction at the temperature for 4-6 hours, cooling after the reaction is completed, filtering, washing with toluene, and drying to obtain adsorption silica gel, and loading the adsorption silica gel into a column to obtain an adsorption column; The specific surface area of ​​the activated silica gel is 500-600m 2 / g, surface hydroxyl density 6.1-8.3μmol / m 2 ; The mass ratio of the activated silica gel, toluene, 3-[(2,3)-epoxypropyloxy]propylmethyldimethoxysilane, and triethylamine is 10:40-60:1-1.5:0.3-0.5; The cyclodextrin is β-cyclodextrin; The mass ratio of cyclodextrin to dimethyl sulfoxide in the cyclodextrin solution is 10:60-80; The mass ratio of modified silica gel to dimethyl sulfoxide in the modified silica gel dispersion is 10:40-50; The mass ratio of the modified silica gel dispersion to the cyclodextrin solution is 1:0.8-1.2; The ratio of the column diameter to the height of the adsorption column is 1:6-10.

[0011] The adsorption and elution method is to flow the mother liquor through the adsorption column at a flow rate of 1-1.5 mL / min, then wash the column with toluene to wash away impurities not bound to the adsorption silica gel, and after washing, elute 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide with an eluent, and collect all the eluent; The mass ratio of adsorbed silica gel to mother liquor in the adsorption column is 1:2-2.5; The eluent is a mixture of acetonitrile, methanol and water; The mass ratio of acetonitrile, methanol and water in the eluent is 20:50-60:3-4; The mass ratio of adsorption silica gel to eluent in the adsorption column is 100:15-20.

[0012] The eluent treatment method is to perform reduced pressure distillation on the collected eluent at 35-40° C. and a vacuum degree of 30-50 mmHg to evaporate excess eluent, wash the obtained precipitate with methanol, and dry it in a vacuum drying oven for 4-5 hours to obtain a primary purified product.

[0013] The crystallization purification method comprises the following steps: heating a first portion of ethyl tert-butyl ether to 45-50° C., adding a primary purified product until the solution is saturated, heating the solution to boiling, dripping cyclohexane therein, stopping dripping when the solution starts to become turbid, adding a second portion of ethyl tert-butyl ether, allowing the solution to stand, cooling at 8-10° C. / h, adding 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals when the solution is cooled to 30-35° C., cooling at 4-5° C. / h to precipitate crystals, washing the obtained crystals with cold methanol for 1-2 times, then washing with cyclohexane for 2-3 times, and drying in a vacuum drying oven for 6-8 hours to obtain high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide; The mass ratio of the first portion of ethyl tert-butyl ether to the second portion of ethyl tert-butyl ether is 100:1.6-2; The temperature of the cold methanol is 0-5°C; The purity of the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is ≥99.5%; The mass ratio of the primary purified product to the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystal particles is 100:0.4-0.8.

[0014] Compared with the prior art, the present invention has the following beneficial effects: The purification method of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide of the present invention has good impurity removal effect, the obtained product has the appearance of white crystals, the yield is 85.7-87.8%, the final purity is 99.81-99.90%, and the melting point range is narrow, which is close to the standard melting point. DETAILED DESCRIPTION

[0015] In order to have a clearer understanding of the technical features, purposes and effects of the present invention, the specific implementation methods of the present invention are now described.

[0016] Example 1 A method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide comprises the following steps: (1) dissolving Dissolve 10 g of crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide in 80 g of toluene, add 4 g of activated carbon for decolorization, and filter to remove insoluble impurities and activated carbon to obtain a mother liquor; The purity of the crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is 90.72%.

[0017] (2) Purification by adsorption column The following steps are involved: A. Preparation of adsorption column Disperse 100 g of activated silica gel in 400 g of toluene, add 10 g of 3-[(2,3)-epoxypropyloxy]propylmethyldimethoxysilane and 3 g of triethylamine, heat to 90°C under nitrogen atmosphere, stir and react for 6 h, filter after the reaction, wash with toluene, and dry to obtain modified silica gel; dissolve 100 g of β-cyclodextrin in 600 g of dimethyl sulfoxide, add sodium hydroxide to pH 13, mix well and let stand for 6 h to obtain a cyclodextrin solution, disperse 100 g of modified silica gel in 400 g of dimethyl sulfoxide to obtain a modified silica gel dispersion, add 600 g of cyclodextrin solution to the modified silica gel dispersion, heat to 100°C, stir and react at this temperature for 4 h, cool, filter, wash with toluene, and dry to obtain adsorption silica gel, and load the adsorption silica gel into a column to obtain an adsorption column; The specific surface area of ​​the activated silica gel is 500m2 / g, surface hydroxyl density 6.1μmol / m 2 ; The ratio of the column diameter to the height of the adsorption column is 1:6.

[0018] B. Adsorption and elution The mother liquor was passed through the adsorption column at a flow rate of 1 mL / min, and the column was then washed with toluene to remove impurities not bound to the adsorption silica gel. After washing, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide was eluted with an eluent, and all the eluent was collected; The mass ratio of adsorbed silica gel to mother liquor in the adsorption column is 1:2; The eluent is a mixture of acetonitrile, methanol and water, and the mass ratio of acetonitrile, methanol and water is 20:50:3; The mass ratio of adsorbed silica gel to eluent in the adsorption column is 100:15.

[0019] C. Eluent Treatment The collected eluate was distilled under reduced pressure at 35°C and a vacuum degree of 30 mmHg to evaporate the excess eluent, and the obtained precipitate was washed with methanol and dried in a vacuum drying oven for 6 hours to obtain a primary purified product.

[0020] (3) Crystallization purification 50 g of ethyl tert-butyl ether was heated to 45° C., and the primary purified product was added until the solution was saturated. The solution was then heated to boiling, and cyclohexane was added dropwise thereto. When the solution began to become turbid, the addition was stopped. Then 0.8 g of ethyl tert-butyl ether was added, and the mixture was allowed to stand and cooled at 8° C. / h. When the mixture was cooled to 30° C., 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals were added, and the mixture was cooled at 4° C. / h to precipitate crystals. The obtained crystals were washed once with cold methanol at 0° C., and then washed twice with cyclohexane, and then dried in a vacuum drying oven for 6 hours to obtain high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. The cooling rate is 5°C / h; The purity of the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is 99.5%; The mass ratio of the primary purified product to the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystal particles is 100:0.4.

[0021] Example 2 A method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide comprises the following steps: (1) dissolving Dissolve 10 g of crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide in 90 g of toluene, add 4.5 g of activated carbon for decolorization, and filter to remove insoluble impurities and activated carbon to obtain a mother liquor; The purity of the crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is 91.64%.

[0022] (2) Purification by adsorption column The following steps are involved: A. Preparation of adsorption column Disperse 100 g of activated silica gel in 500 g of toluene, add 12 g of 3-[(2,3)-epoxypropoxy]propylmethyldimethoxysilane and 4 g of triethylamine, heat to 95° C. under nitrogen atmosphere, stir and react for 5 h, filter after the reaction, wash with toluene, and dry to obtain modified silica gel; dissolve 100 g of β-cyclodextrin in 700 g of dimethyl sulfoxide, add sodium hydroxide to pH 13.5, mix well and let stand for 5 h to obtain a cyclodextrin solution, disperse 100 g of modified silica gel in 450 g of dimethyl sulfoxide to obtain a modified silica gel dispersion, add 550 g of cyclodextrin solution to the modified silica gel dispersion, heat to 105° C., stir and react at this temperature for 5 h, cool, filter, wash with toluene, and dry to obtain adsorption silica gel, and load the adsorption silica gel into a column to obtain an adsorption column; The specific surface area of ​​the activated silica gel is 550 m 2 / g, surface hydroxyl density 7.0μmol / m 2 ; The ratio of the column diameter to the height of the adsorption column is 1:8.

[0023] B. Adsorption and elution The mother liquor was passed through the adsorption column at a flow rate of 1.2 mL / min, and the column was then washed with toluene to remove impurities not bound to the adsorption silica gel. After washing, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide was eluted with an eluent, and all the eluent was collected; The mass ratio of adsorbed silica gel to mother liquor in the adsorption column is 1:2.2; The eluent is a mixture of acetonitrile, methanol and water, and the mass ratio of acetonitrile, methanol and water is 20:55:3.5; The mass ratio of adsorbed silica gel to eluent in the adsorption column is 100:18.

[0024] C. Eluent Treatment The collected eluate was distilled under reduced pressure at 38°C and a vacuum degree of 40 mmHg to evaporate the excess eluent, and the obtained precipitate was washed with methanol and dried in a vacuum drying oven for 4.5 hours to obtain a primary purified product.

[0025] (3) Crystallization purification 50 g of ethyl tert-butyl ether was heated to 48° C., and the primary purified product was added until the solution was saturated. The solution was then heated to boiling, and cyclohexane was added dropwise thereto. When the solution began to become turbid, the addition was stopped. Then 0.9 g of ethyl tert-butyl ether was added, and the mixture was allowed to stand and cooled at 9° C. / h. When the mixture was cooled to 32° C., 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals were added, and the mixture was cooled at 4.5° C. / h to precipitate crystals. The obtained crystals were washed once with 2° C. cold methanol, and then washed three times with cyclohexane, and then dried in a vacuum drying oven for 7 h to obtain high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. The purity of the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is 99.6%; The mass ratio of the primary purified product to the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystal particles is 100:0.6.

[0026] Example 3 A method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide comprises the following steps: (1) dissolving Dissolve 10 g of crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide in 100 g of toluene, add 5 g of activated carbon for decolorization, and filter to remove insoluble impurities and activated carbon to obtain a mother liquor; The purity of the crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is 91.05%.

[0027] (2) Purification by adsorption column The following steps are involved: A. Preparation of adsorption column Disperse 100 g of activated silica gel in 600 g of toluene, add 15 g of 3-[(2,3)-epoxypropoxy]propylmethyldimethoxysilane and 5 g of triethylamine, heat to 100° C. in a nitrogen atmosphere, stir and react for 4 h, filter after the reaction, wash with toluene, and dry to obtain modified silica gel; dissolve 100 g of β-cyclodextrin in 800 g of dimethyl sulfoxide, add sodium hydroxide to a pH of 14, mix well and let stand for 4 h to obtain a cyclodextrin solution, disperse 100 g of modified silica gel in 500 g of dimethyl sulfoxide to obtain a modified silica gel dispersion, add 480 g of cyclodextrin solution to the modified silica gel dispersion, heat to 110° C., stir and react at this temperature for 4 h, cool after the reaction, filter, wash with toluene, and dry to obtain adsorption silica gel, and load the adsorption silica gel into a column to obtain an adsorption column; The specific surface area of ​​the activated silica gel is 600m 2 / g, surface hydroxyl density 8.3μmol / m 2 ; The ratio of the column diameter to the height of the adsorption column is 1:10.

[0028] B. Adsorption and elution The mother liquor was passed through the adsorption column at a flow rate of 1.5 mL / min, and the column was then washed with toluene to remove impurities not bound to the adsorption silica gel. After washing, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide was eluted with an eluent, and all the eluent was collected; The mass ratio of adsorbed silica gel to mother liquor in the adsorption column is 1:2.5; The eluent is a mixture of acetonitrile, methanol and water, and the mass ratio of acetonitrile, methanol and water is 20:60:4; The mass ratio of adsorbed silica gel to eluent in the adsorption column is 100:20.

[0029] C. Eluent Treatment The collected eluate was distilled under reduced pressure at 40°C and a vacuum degree of 50 mmHg to evaporate the excess eluent, and the obtained precipitate was washed with methanol and dried in a vacuum drying oven for 5 hours to obtain a primary purified product.

[0030] (3) Crystallization purification 50 g of ethyl tert-butyl ether was heated to 50° C., and the primary purified product was added until the solution was saturated. The solution was then heated to boiling, and cyclohexane was added dropwise thereto. When the solution began to become turbid, the addition was stopped. Then 1 g of ethyl tert-butyl ether was added, and the mixture was allowed to stand and cooled at 10° C. / h. When the mixture was cooled to 35° C., 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals were added, and the mixture was cooled at 5° C. / h to precipitate crystals. The obtained crystals were washed twice with 5° C. cold methanol, and then washed three times with cyclohexane, and then dried in a vacuum drying oven for 8 h to obtain high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. The purity of the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is 99.6%; The mass ratio of the primary purified product to the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystal particles is 100:0.8.

[0031] Comparative Example 1 Comparative Example 1 adopts the purification method of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide described in Example 2, except that the adsorption column purification method is different, and the other steps are the same; The adsorption column purification method was changed to: The adsorption column purification comprises the following steps: passing through the adsorption column, treating the column liquid; A. Pass the mother liquid through the adsorption column at a flow rate of 1.2 mL / min, and collect all the liquid passing through the column; The adsorption column is filled with activated silica gel, and the specific surface area of ​​the activated silica gel is 550m 2 / g, surface hydroxyl density 7.0μmol / m 2 ; The ratio of the column diameter to the height of the adsorption column is 1:8.

[0032] B. Column Liquid Treatment The collected column liquid was distilled under reduced pressure at 45°C and a vacuum degree of 40 mmHg to evaporate excess toluene, and the obtained precipitate was washed with ethanol and dried in a vacuum drying oven for 5 hours to obtain a primary purified product.

[0033] The purity of the crude product of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide used in Comparative Example 1 is 90.33%.

[0034] Comparative Example 2 Comparative Example 2 adopts the purification method of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide described in Example 2, except that in the step of preparing the adsorption column, γ-cyclodextrin is used instead of β-cyclodextrin, and the remaining steps are the same; The purity of the crude product of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide used in Comparative Example 2 was 90.56%.

[0035] Comparative Example 3 Comparative Example 3 adopts the purification method of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide described in Example 2, except that, in the crystallization purification step, toluene is used instead of ethyl tert-butyl ether, and the addition of cyclohexane and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is omitted. The modified crystallization purification step is: Heat 50g of toluene to boiling, add the primary purified product until the solution is saturated, place it, and cool it at a rate of 4.5°C / h to precipitate crystals. The obtained crystals are washed once with 2°C cold methanol, then washed three times with cyclohexane, and then dried in a vacuum drying oven for 7h to obtain high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide; The purity of the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is 99.6%; The mass ratio of the primary purified product to the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystal particles is 100:0.6.

[0036] Comparative Example 3 uses a crude product of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide with a purity of 91.17%. The high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide prepared in Example 1-3 and Comparative Example 1-3 was subjected to product quality testing, including the appearance, yield, purity, and melting point of the product. The purity of the product was detected by high performance liquid chromatography, and the melting point was determined by an automatic melting point meter. The measurement results are shown in Table 1.

[0037] Table 1 Product quality test results

[0038] It can be seen from the above test results that the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide prepared by the methods of Examples 1-3 and Comparative Examples 1 and 3 is a white crystal, and the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide prepared by the method of Comparative Example 2 is a light yellow crystal; The purity of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide prepared in Examples 1-3 is higher than that in Comparative Examples 1-3, the melting point range is narrower, and it is closer to the standard melting point. The yield of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide prepared in Comparative Example 2 is closer to the value of Example 2.

[0039] The invention firstly dissolves the crude product in toluene, adds activated carbon for adsorption and decolorization, and uses an adsorption column to adsorb 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide into the mother liquor after decolorization. The beta-cyclodextrin bonded on the silica gel has a cavity structure, the size of the cavity is about 0.78nm, which is close to the molecular size of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, and the matching degree is high. The cavity of the beta-cyclodextrin is hydrophobic inside and hydrophilic outside the cavity. The hydrophobicity of the cavity part can be compatible with that of 9,10-dihydro- The hydrophobic part of the benzene ring of 9-oxa-10-phosphaphenanthrene-10-oxide undergoes inclusion complexation, while the polar group PH of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide can undergo polar interactions such as hydrogen bonds with the hydroxyl groups at the edge of the cavity of the cyclodextrin molecule. 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide can form a stable inclusion complex with β-cyclodextrin through hydrophobic and polar interactions, thereby achieving the adsorption of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide.

[0040] The eluent used in the elution process is composed of acetonitrile, methanol and water. Acetonitrile has high elution strength and can dissolve 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. Methanol enhances the elution efficiency by competitively binding to the hydroxyl group of cyclodextrin. By controlling the ratio of acetonitrile, methanol and water, balancing the hydrophobic effect and polarity matching, the selective elution of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is achieved, thereby improving the elution efficiency.

[0041] Due to the specific size of the cavity structure of β-cyclodextrin, molecules larger than the cavity structure cannot enter the cavity, and thus cannot form inclusion complexes with β-cyclodextrin. The molecular size of the macromolecular impurities formed by intermolecular dehydration during the preparation of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is larger than the cavity size of β-cyclodextrin, and cannot form inclusion complexes with β-cyclodextrin, and will not be adsorbed by the adsorption column. Therefore, these macromolecular impurities can be removed in the adsorption column purification step.

[0042] The primary purified product after purification by the adsorption column contains, in addition to 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, small molecular substances such as 2-hydroxybiphenyl-2-hypophosphorous acid and o-phenylphenol, which are close in molecular size to 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. In order to further remove these substances, the present invention provides a crystallization purification step after the adsorption column purification step.

[0043] In the crystallization purification step, ethyl tert-butyl ether has a large solubility for 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, while cyclohexane has a small solubility for 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide. After dissolving the primary purified product with ethyl tert-butyl ether, the solvent's solubility is gradually reduced by dripping cyclohexane, which promotes the selective precipitation of the target product and reduces the coprecipitation of impurities. After dissolving in a boiling state, a small amount of ethyl tert-butyl ether is added to adjust the supersaturation to avoid excessively fine grains or impurity encapsulation caused by rapid nucleation. When gradually cooling from a boiling state to 30-35°C, seed crystals are added to induce directional crystallization using the characteristics of the metastable zone to avoid uneven crystals caused by spontaneous nucleation. The solvent combination and seed crystal induction used in this step play a synergistic role, improving the purification efficiency and crystal purity of the target product.

[0044] Comparative Example 1 is based on Example 2. In the step of preparing the adsorption column, an adsorption column filled with active silica gel is used to adsorb polar impurities in the mother liquor. The yield of the prepared high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is lower than that of Example 2. This may be because 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide is polar, and the adsorption column will adsorb a small amount of target product while adsorbing polar impurities, resulting in a lower final yield; the purity of the product in Comparative Example 1 is also lower than that in Example 2, and the melting point range is larger, reflecting that the silica gel column has limited effect on impurity removal by adsorption, and some impurities with physical properties similar to the target product cannot be removed, resulting in reduced product purity.

[0045] Comparative Example 2 is based on Example 2, and in the step of preparing the adsorption column, γ-cyclodextrin is used instead of β-cyclodextrin. The cavity structure size of γ-cyclodextrin is larger than that of β-cyclodextrin, which will cause impurities with molecular size larger than the target product to be adsorbed on γ-cyclodextrin and cannot be removed in the adsorption column purification step. In the crystallization purification step, due to the similar molecular structure, they cannot be completely removed, thereby reducing the purity of the target product.

[0046] Comparative Example 3 is based on Example 2, in the crystallization purification step, toluene is used instead of ethyl tert-butyl ether, and the addition of cyclohexane is omitted. Toluene has good solubility for 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide and other impurities with similar physical properties. When the temperature is reduced for crystallization, these impurities will be entrained into the crystals, resulting in a decrease in the purification effect.

[0047] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, characterized in that: The purification method comprises the following steps: dissolution, purification by adsorption column, and purification by crystallization; The adsorption column purification method comprises preparing the adsorption column, adsorption and elution, and eluent treatment; The method for preparing the adsorption column comprises the following steps: dispersing activated silica gel in toluene, adding 3-[(2,3)-epoxypropyloxy]propylmethyldimethoxysilane and triethylamine, heating to 90-100° C. in a nitrogen atmosphere, stirring for reaction for 4-6 hours, filtering after the reaction is completed, washing with toluene, and drying to obtain modified silica gel; dissolving cyclodextrin in dimethyl sulfoxide, adding sodium hydroxide until the pH value is 13-14, mixing evenly, and standing for 4-6 hours to obtain a cyclodextrin solution, dispersing the modified silica gel in dimethyl sulfoxide to obtain a modified silica gel dispersion, adding the cyclodextrin solution to the modified silica gel dispersion, heating to 100-110° C., stirring for reaction at the temperature for 4-6 hours, cooling after the reaction is completed, filtering, washing with toluene, and drying to obtain adsorption silica gel, and loading the adsorption silica gel into a column to obtain the adsorption column.

2. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 1, characterized in that: In the step of preparing the adsorption column, The specific surface area of ​​the activated silica gel is 500-600m 2 / g, surface hydroxyl density 6.1-8.3μmol / m 2 ; The mass ratio of the activated silica gel, toluene, 3-[(2,3)-epoxypropyloxy]propylmethyldimethoxysilane, and triethylamine is 10:40-60:1-1.5:0.3-0.5; The cyclodextrin is β-cyclodextrin; The mass ratio of cyclodextrin to dimethyl sulfoxide in the cyclodextrin solution is 10:60-80.

3. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 1, characterized in that: In the step of preparing the adsorption column, The mass ratio of modified silica gel to dimethyl sulfoxide in the modified silica gel dispersion is 10:40-50; The mass ratio of the modified silica gel dispersion to the cyclodextrin solution is 1:0.8-1.2; The ratio of the column diameter to the height of the adsorption column is 1:6-10.

4. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 1, characterized in that: The adsorption and elution method comprises the following steps: passing the mother liquor through the adsorption column at a flow rate of 1-1.5 mL / min, washing the column with toluene to remove impurities not combined with the adsorption silica gel, and after washing, eluting 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide with an eluent, and collecting all the eluents.

5. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 4, characterized in that: In the adsorption and elution steps, The mass ratio of adsorbed silica gel to mother liquor in the adsorption column is 1:2-2.5; The eluent is a mixture of acetonitrile, methanol and water; The mass ratio of acetonitrile, methanol and water in the eluent is 20:50-60:3-4; The mass ratio of adsorption silica gel to eluent in the adsorption column is 100:15-20.

6. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 1, characterized in that: The eluent treatment method is to perform reduced pressure distillation on the collected eluent at 35-40° C. and a vacuum degree of 30-50 mmHg to evaporate excess eluent, wash the obtained precipitate with methanol, and dry it in a vacuum drying oven for 4-5 hours to obtain a primary purified product.

7. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 1, characterized in that: The crystallization purification method comprises the following steps: heating the first portion of ethyl tert-butyl ether to 45-50° C., adding the primary purified product until the solution is saturated, heating the solution to boiling, dripping cyclohexane therein, stopping dripping when the solution starts to become turbid, adding the second portion of ethyl tert-butyl ether, allowing the solution to stand, cooling at 8-10° C. / h, adding 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals when the solution is cooled to 30-35° C., cooling at 4-5° C. / h to precipitate crystals, washing the obtained crystals with cold methanol for 1-2 times, then washing with cyclohexane for 2-3 times, and drying them in a vacuum drying oven for 6-8 hours to obtain high-purity 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide.

8. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 7, characterized in that: In the crystallization purification step, The mass ratio of the first portion of ethyl tert-butyl ether to the second portion of ethyl tert-butyl ether is 100:1.6-2; The temperature of the cold methanol is 0-5°C; The purity of the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystals is ≥99.5%; The mass ratio of the primary purified product to the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide crystal particles is 100:0.4-0.

8.

9. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 1, characterized in that: The dissolving method comprises dissolving the crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide in toluene, adding activated carbon for decolorization, filtering to remove insoluble impurities and activated carbon, and obtaining a mother liquor.

10. The method for purifying 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide according to claim 9, characterized in that: In the dissolving step, the mass ratio of crude 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, toluene and activated carbon is 10:80-100:4-5.

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