Process for the preparation of a class of high purity aromatic phosphine oxides

Abstract

The application belongs to the technical field of organic semiconductor material application, and discloses a preparation method of high-purity aromatic phosphine oxide compounds, a structural formula of which is as formula I (formula I). The main process of the purification and preparation of the compounds comprises: (1) coupling reaction of aryl phosphine oxide borate and bromoaryl derivative Br-R2; (2) the polarity of Br-R2 is smaller than that of the target product (formula I), and Br-R2 is removed through column chromatography separation; (3) aiming at the coupling crude product obtained in (1) and (2), the residual aryl phosphine oxide borate derivative is converted into an easily separated phenol derivative through the synergistic effect of a peroxide oxidizing agent and an alkali, so that the purpose of purification and separation is achieved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic semiconductor material application, and particularly relates to a preparation method of high-purity aromatic phosphine oxide compounds. BACKGROUND

[0002] The aryl phosphine oxide group can be used to construct amorphous organic functional materials due to its rigid and stereoscopic molecular structure and strong electron-withdrawing property, and also exhibits reversible electrochemical reduction properties. A preparation method of a functional compound containing a triaryl phosphine oxide and a nitrogen heterocyclic group is disclosed in Chinese patent CN103374040B, that is, aryl phosphine oxide borate and halogenated nitrogen-containing heterocycle are coupled through Suzuki reaction. In the above reaction, the polarity of aryl phosphine oxide borate and aryl phosphine oxide product may be similar, which leads to difficulty in separation; in addition, the hydrolysis product aryl phosphine oxide borate of aryl phosphine oxide borate may form potential oligomeric condensates, which is not conducive to separation and purification. SUMMARY

[0003] In order to overcome the shortcomings and deficiencies of the prior art, the primary purpose of the present application is to provide a preparation method of high-purity aromatic phosphine oxide compounds.

[0004] The aryl phosphine oxide borate is used for coupling reaction with halogenated aromatic hydrocarbon or halogenated heteroaromatic hydrocarbon Br-R2, so that the functional compound containing aryl phosphine oxide (formula I, ) can be conveniently obtained. The present application proposes that the residual aryl phosphine oxide borate and its boronic acid derivative are converted into the corresponding phenol derivative by the synergistic effect of peroxide oxidant and base, so as to achieve the purification target.

[0005] Another purpose of the present application is to provide high-purity aromatic phosphine oxide compounds prepared by the above method.

[0006] The purpose of the present application is realized by the following scheme:

[0007] The preparation method of the high-purity aromatic phosphine oxide compounds is as follows:

[0008]

[0009] X is Cl, Br or I;

[0010] R1 and R2 are aryl, heteroaryl, substituted aryl or substituted heteroaryl;

[0011] m=1-6; when m is greater than or equal to 2, R1 can be the same or different; the polarity of Br-R2 is less than that of the aryl phosphine oxide product (formula I);

[0012] The R1 is any one of the following representative structural units: ​

[0013]

[0014] wherein R3 and R4 are alkyl, aryl, heteroaryl, substituted aryl and substituted heteroaryl, or can form a cyclic structure.

[0015] said R2 is substituted or unsubstituted aryl and heteroaryl, and is any one of the following representative structural units:

[0016]

[0017]

[0018] wherein R5 is substituted or unsubstituted aryl and heteroaryl.

[0019] According to the above preparation method, comprising the following steps:

[0020] (1) using diphenyl (monohaloaryl) phosphine as raw material, by hydrogen peroxide oxidation, to obtain diphenyl (monobromoaryl) phosphine oxide intermediate

[0021] (2) diphenyl (monobromoaryl) phosphine oxide obtained in step (1) by palladium-catalyzed boronic esterification, to obtain diphenyl aryl phosphine oxide boronic ester intermediate s;

[0022] (3) diphenyl aryl phosphine oxide boronic ester obtained in step (2) and bromoaryl derivative Br-R2, by Suzuki coupling reaction, to obtain the crude product of aryl phosphine oxide compound .

[0023] (4) for the crude product obtained in step (3), separated by flash column chromatography, to remove Br-R2;

[0024] (5) the aryl phosphine oxide-containing compound obtained in step (4) by removing Br-R2 is dissolved in an organic solvent, and a peroxide oxidant / alkali is added to convert the residual aryl phosphine oxide borate and its boronic acid derivative into the corresponding phenolic derivative;

[0025] (6) using further post-processing process, including column chromatography, solvent washing, recrystallization and sublimation, to obtain high-purity aromatic phosphine oxide compound.

[0026] Preferably, the molar ratio of diphenyl (monobromoaryl) phosphine to hydrogen peroxide in step (1) is 1:3-6.

[0027] Preferably, the coupling reaction in step (2) is a Suzuki coupling reaction after mixing the diphenyl (monobromo aryl) phosphine oxide with a palladium catalyst and pinacol diboronic acid.

[0028] Preferably, the molar ratio of the diphenyl (monobromo aryl) phosphine oxide to the palladium catalyst and pinacol diboronic acid is 1:0.01-0.03:1-3.

[0029] Preferably, the molar ratio of the diphenyl aryl phosphine oxide borate to the bromo aryl derivative in step (3) is 1:1-1.3.

[0030] Preferably, the temperature of the Suzuki coupling reaction in step (3) is 70-100℃, and the reaction time is 1-24h.

[0031] Preferably, the eluent of the column chromatography in step (4) is a mixed solvent of dichloromethane or toluene, xylene and ethyl acetate, methanol, ethanol, isopropanol.

[0032] Preferably, the specific process in step (5) is: dissolving the coupling product without Br-R2 in an organic solvent, then adding a peroxide oxidant and stirring, and then adding an alkali solution and stirring.

[0033] Preferably, the organic solvent in step (5) is a mixed solvent of dichloromethane and an alcohol, and the alcohol is at least one of ethanol, methanol and isopropanol.

[0034] Preferably, the molar ratio of the aryl phosphine oxide-containing compound to the peroxide oxidant in step (5) is 1:1-20.

[0035] Preferably, the molar ratio of the peroxide oxidant to the alkali in step (5) is 1:1-20.

[0036] Preferably, the peroxide oxidant used in step (5) is hydrogen peroxide, sodium peroxide, potassium peroxide, di-tert-butyl peroxide, peracetic acid, benzoyl peroxide, etc.

[0037] Preferably, the alkali used in step (5) is a hydroxide, such as sodium hydroxide, potassium hydroxide.

[0038] Preferably, the eluent of the column chromatography in step (6) is a mixed solvent of dichloromethane or toluene, xylene and ethyl acetate, methanol, ethanol, isopropanol.

[0039] Preferably, the sublimation in step (6) is gradient temperature sublimation purification, and the gradient sublimation temperature ranges are 150-300℃ and 250-400℃, respectively.

[0040] Compared with the prior art, the present application has the following advantages and beneficial effects:

[0041] (1) The method for purifying and preparing aryl phosphine oxide compounds, which converts residual aryl phosphine oxide borate and its borate derivatives into corresponding phenol derivatives, so as to achieve the purpose of separation and purification;

[0042] (2) The method for purifying and preparing aryl phosphine oxide compounds, which quantitatively converts aryl phosphine oxide borate and its borate derivatives into corresponding phenol derivatives by the synergistic effect of "peroxide" and strong base, and the conversion yield reaches or approaches 100%;

[0043] (3) The method for purifying and preparing aryl phosphine oxide compounds provided by the application can realize the large-scale synthesis of high-purity aryl phosphine oxide compounds. BRIEF DESCRIPTION OF DRAWINGS

[0044] Figure 1 ESI-MS mass spectrum of 3-(diphenyl phosphine) phenol;

[0045] Figure 2 NMR spectrum of aryl phosphine oxide compound PO1 after purification and refinement in the embodiment of the application, and the solvent is deuterated dichloromethane;

[0046] Figure 3 HPLC spectrum of compound PO1 after purification and refinement;

[0047] Figure 4 NMR spectrum of aryl phosphine oxide compound PO2 after purification and refinement in the embodiment of the application, and the solvent is deuterated dimethyl sulfoxide;

[0048] Figure 5 HPLC spectrum of compound PO2 after purification and refinement;

[0049] Figure 6 NMR spectrum of aryl phosphine oxide compound PO3 after purification and refinement in the embodiment of the application, and the solvent is deuterated dimethyl sulfoxide;

[0050] Figure 7 HPLC spectrum of compound PO3 after purification and refinement;

[0051] Figure 8 NMR spectrum of aryl phosphine oxide compound PO4 after purification and refinement in the embodiment of the application, and the solvent is deuterated dichloromethane;

[0052] Figure 9 HPLC spectrum of compound PO4 after purification and refinement;

[0053] Figure 10 NMR spectrum of aryl phosphine oxide compound PO5 after purification and refinement in the embodiment of the application, and the solvent is deuterated dichloromethane;

[0054] Figure 11 HPLC profile of compound PO5 after purification and polishing. DETAILED DESCRIPTION

[0055] The present application is further described in detail by the following examples and drawings, but the embodiments of the present application are not limited thereto. In the examples, the specific conditions not mentioned are carried out according to the conventional conditions or the conditions recommended by the manufacturers. The reagents or instruments used are not specified by the manufacturers, and are all conventional products that can be purchased on the market.

[0056] Experimental exploration process:

[0057]

[0058] Diphenyl[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]phosphine oxide (100 mg, 0.25 mmol) was dissolved in dichloromethane (30 mL), and hydrogen peroxide aqueous solution (15 eq. 3.75 mmol) and ethanol (1 mL) were added, and stirred at room temperature. Then, sodium hydroxide aqueous solution (45 eq. 3M) was added. Immediately, TLC detection showed that "diphenyl[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]phosphine oxide" was not detected. The reaction was stopped, and sodium bisulfite aqueous solution was added to quench the excess hydrogen peroxide, followed by extraction with dichloromethane, and the organic layer was collected and back-extracted with water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure and separated by column chromatography with dichloromethane and ethanol mixed solvent (100:1 v / v) as eluent to obtain white solid 3-(diphenylphosphoryl)phenol (69 mg), with a yield of 95%. HRMS (ESI, negative ion mode) m / z: [M-H + ] - : C 18 H 14 O2P calculated: 293.0731; found: 293.0756 (100%).

[0059] The Rf value of diphenyl[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]phosphine oxide was 0.3, while the Rf value of 3-(diphenylphosphoryl)phenol was reduced to 0.05, using dichloromethane:ethanol (100:1 v / v) as the developing agent. TLC detection showed that aryl phosphine oxide borate was converted into the corresponding phenol derivative, and the polarity increased, which was mainly due to the strong electron-withdrawing effect of the P=O group.

[0060] Figure 1 ESI-MS mass spectrum of 3-(diphenylphosphoryl)phenol (negative ion mode).

[0061] The five compounds prepared by the purification method in the present application have the following chemical formula:

[0062]

[0063]

[0064] Example 1

[0065] The specific synthesis steps of the compound PO1 described in this Example 1 are as follows:

[0066] Step one: preparation of (3-bromophenyl)diphenylphosphine oxide (compound 1)

[0067]

[0068] To a solution of (3-bromophenyl)diphenylphosphine (12.3 g, 36 mmol) in dichloromethane (60 mL) was added hydrogen peroxide (15 mL) and ethanol (15 mL). The reaction was stirred at room temperature overnight. When the reaction was completed, the reaction mixture was poured into an aqueous sodium sulfite solution to reduce the excess hydrogen peroxide. Then, the organic layer was extracted with dichloromethane and back-extracted with water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure and separated by column chromatography with dichloromethane and ethanol as the eluent to obtain a white solid with a yield of 97% (12.5 g).

[0069] 1 H NMR (400 MHz, DMSO) δ 7.86 (d, J = 7.8 Hz, 1H), 7.74 (d, J = 11.7 Hz, 1H), 7.49 - 7.67 (m, 12H).

[0070] Step two: preparation of diphenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide (compound 2)

[0071]

[0072] Pd(dppf)Cl2(254 mg, 0.35 mmol) was added to the reaction mixture of (3- bromophenyl)diphenylphosphine oxide (12.5 g, 35 mmol), bis(pinacolato)diboron (10.6 g, 42 mmol), potassium acetate (10.3 g, 105 mmol), 1,4-dioxane (200 mL) under N2atmosphere. The reaction was heated to 80 °C. After 12 h, the reaction was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was extracted with dichloromethane and water. The collected organic layer was back extracted with water, dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography using dichloromethane and ethanol (100:1 v / v) as eluents to give a white solid (13.4 g, 95% yield).

[0073] 1 H NMR (400 MHz, DMSO) δ 8.08 (d, J = 11.8 Hz, 1H), 7.90 (dd, J = 7.3, 1.3 Hz, 1H), 7.53 - 7.66 (m, 12H), 1.28 (s, 12H).

[0074] Step three: Preparation of compound PO1

[0075]

[0076] Pd(PPh3)4(29 mg, 0.0247 mmol) was added to the reaction mixture of 9-bromo-10-(4-(phenanthren-9-yl)phenyl)anthracene (1.6 g, 3.21 mmol), diphenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide (1 g, 2.47 mmol), aqueous sodium carbonate (2 M, 7.41 mmol), toluene (40 mL), ethanol (9 mL) under N2atmosphere. The reaction was heated to 90 °C and stirred overnight. After cooling to room temperature, water was added, and the organic layer was separated and back extracted with water. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography using dichloromethane (to remove 9-bromo-10-(4-(phenanthren-9-yl)phenyl)anthracene), dichloromethane and ethanol (100:1 v / v) as eluents. For the sample purified by column chromatography, further washing with alcoholic solvents gave a white solid (1.19 g).

[0077] 1 H NMR (500 MHz, Methylene Chloride-d2 Figure 2) δ 8.86 (dd, J = 8.4, 1.3 Hz, 1H), 8.80 (d, J = 8.2 Hz, 1H), 8.21 (dd, J = 8.2, 1.3 Hz, 1H), 8.01 (dd, J = 7.7, 1.5 Hz, 1H), 7.97 - 7.86 (m, 4H), 7.83 - 7.53 (m, 19H), 7.50 (m, 4H), 7.45 - 7.37 (m, 4H).

[0078] Step four: purification of compound POl

[0079] (1) Chemical treatment: The crude product obtained from column chromatography in step three above was dissolved in dichloromethane (100 mL), and hydrogen peroxide aqueous solution (1 eq.) and ethanol (5 mL) were added, and stirred at room temperature. Then, sodium hydroxide aqueous solution (3 eq. 3M) was added, and stirred for 30 min. Sodium bisulfite aqueous solution was added to quench the excess hydrogen peroxide. Then, dichloromethane was used to extract, and the organic layer was collected, and then back-extracted with water. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The product obtained from column chromatography was dissolved in dichloromethane, and ethanol was added to precipitate the solid. Then, the mixture was heated and stirred under reflux for 12 h, filtered while hot, and the filter cake was dried.

[0080] The Rf value of 3-(diphenylphosphinoyl)phenol was about 0.05, and the Rf value of POl was about 0.25, using dichloromethane:ethanol (100:1 v / v) as the developing agent, so that the column chromatography separation was achieved.

[0081] (2) Sublimation purification. The filter cake was subjected to gradient temperature sublimation. HPLC detection showed that the HPLC purity of POl was 99.94% ( Figure 3 ).

[0082] Example 2

[0083] The specific synthesis steps of compound PO2 in this example 2 are as follows:

[0084] The diphenyl(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide in this example 2 is the same as that in example 1.

[0085] Step one: preparation of compound PO2:

[0086]

[0087] To a solution of compound POl (1.0 g, 1.0 mmol) in 50 mL of toluene, was added 4,4,5,5-tetramethyl-2-(2-oxoethyl)-2H-l,3,2-dioxaborolane (0.5 mL, 2.5 mmol), potassium acetate (0.5 g, 5.0 mmol) and Pd(PPh3)4(0.1 g, 0.1 mmol) under N2atmosphere. The reaction mixture was heated to 90 °C and stirred for 12 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure. The residue was purified by column chromatography using dichloromethane and ethanol (100:1 v / v) as eluent to give compound PO2 as a white solid in 55% yield (0.55 g).

[0088] 1 H NMR (500 MHz, DMSO-d6 Figure 4 ) δ 8.73-8.64 (m, 4H), 7.96 (m, 1H), 7.93-7.86 (m, 2H), 7.85-7.74 (m, 6H), 7.71-7.56 (m, 17H), 7.51-7.44 (m, 4H).

[0089] Step two: purification process of compound PO2:

[0090] (1) Chemical treatment process: The crude product from column chromatography in step one was dissolved in dichloromethane (100 mL) and hydrogen peroxide (1 eq.) and ethanol (5 mL) were added. The mixture was stirred at room temperature. Then, sodium hydroxide (3 eq. 3M) was added and the stirring was continued. The reaction was stopped when TLC showed no presence of boronic ester starting material. Sodium bisulfite solution was added to quench the excess hydrogen peroxide. The mixture was extracted with dichloromethane and the organic layer was collected and back extracted with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure. The residue was purified by column chromatography using dichloromethane and ethanol (100:1 v / v) as eluent to give a light yellow solid. The product from column chromatography was dissolved in dichloromethane and ethanol was added to precipitate the solid. The mixture was heated and stirred under reflux for 12 h, filtered hot and the filter cake was dried.

[0091] The Rf value of 3-(diphenylphosphinoyl)phenol is about 0.05 and the Rf value of PO2 is about 0.25 using dichloromethane:ethanol (100:1 v / v) as the eluent, thus achieving column chromatography separation.

[0092] (2) Sublimation purification. The obtained filter cake was subjected to gradient temperature sublimation to obtain the product. The HPLC purity of PO2 was 99.95% (HPLC detection). Figure 5

[0093] Example 3

[0094] The specific synthesis steps of the compound PO3 described in this Example 3 are as follows:

[0095] The diphenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide in this Example 3 is the same as the preparation step in Example 1.

[0096] Step one: preparation of compound PO3:

[0097]

[0098] Under N2 atmosphere, tetrakis(triphenylphosphine)palladium (12 mg) was added to a mixture of diphenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide (405 mg, 1.001 mmol), 2-(3-bromophenyl)-4,6-diphenyl-1,3,5-triazine (505 mg, 1.300 mmol), ethanol (4 ml) and aqueous sodium carbonate solution (2 M, 4 ml) in toluene (30 ml), and stirred at 90°C for 12 hours; after cooling to room temperature, water was added, the organic layer was separated, and then back-extracted with water. The obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure and column chromatography separation was performed using dichloromethane (to remove residual 2-(3-bromophenyl)-4,6-diphenyl-1,3,5-triazine), a mixture of dichloromethane and ethanol (100:1 v / v) as eluent; for the sample separated by column chromatography, or further washed with an alcohol solvent to obtain white solid compound PO3 with a yield of 70% (412 mg).

[0099] 1 H NMR (500 MHz, DMSO-d6 Figure 6 ) δ 8.82 (t, J = 1.8 Hz, 1H), 8.73 (m, 5H), 8.08 (m, 1H), 8.01-7.90 (m, 2H), 7.81-7.70 (m, 9H), 7.70-7.63 (m, 6H), 7.63-7.57 (m, 4H). HPLC = 99.95% ​

[0100] Step II: Purification of compound PO3:

[0101] (1) Chemical treatment: The crude product from step I above was dissolved in dichloromethane (100 mL) and hydrogen peroxide (1 eq.) in water and ethanol (5 mL) was added. The reaction mixture was stirred at room temperature. Subsequently, sodium sulfite (3 eq.) in water was added and the reaction was continued. The reaction was monitored by TLC and stopped when the starting boronate was no longer present. The excess hydrogen peroxide was quenched by the addition of sodium sulfite solution. The organic layer was collected and back extracted with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent was removed under reduced pressure. The product was purified by column chromatography using dichloromethane and ethanol (100:1 v / v) as eluent to obtain a white solid. The product from column chromatography was dissolved in dichloromethane and isopropanol was added to precipitate the solid. The solid was then heated and stirred under reflux for 12 h, filtered hot and dried.

[0102] Column chromatography was performed using 3-(diphenylphosphinoyl)phenol with an Rf of ~0.05 and PO2 with an Rf of ~0.25 using dichloromethane:ethanol (100:1 v / v) as the eluent.

[0103] (2) Sublimation purification: The sample from step I above was subjected to gradient temperature sublimation to obtain the product. The HPLC purity of PO3 was 99.95% (HPLC). Figure 7 ).

[0104] Example 4

[0105] The specific synthesis of compound PO4 according to this Example 4 is as follows:

[0106] The preparation of diphenyl(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide in this Example 4 is the same as in Example 1.

[0107] Step I: Preparation of compound PO4

[0108]

[0109] Pd(PPh3)4(33 mg, 0.029 mmol) was quickly added to a mixture of 3-bromo-9- phenyl-6-(9-phenylcarbazol-3-yl)carbazole (1.71 g, 3.03 mmol), diphenyl(3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide (1.17 g, 2.89 mmol), and potassium carbonate (2 M, 8.67 mmol) in a mixture of toluene (100 mL) and ethanol (25 mL) under nitrogen and heated to 90 °C overnight. After cooling to room temperature, water was added, the organic layer was separated, and the aqueous layer was back-extracted with water. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography using dichloromethane (to remove residual 3-bromo-9-phenyl-6-(9-phenylcarbazol-3-yl)carbazole), then a mixture of dichloromethane and ethanol (100:1 v / v) as eluents to give 1.85 g (84%) of a white solid.

[0110] 1 H NMR (500 MHz, Methylene Chloride-d2 Figure 8 ) δ 8.53 (d, J = 1.7 Hz, 1H), 8.52 - 8.49 (m, 1H), 8.47 (d, J = 1.8 Hz, 1H), 8.25 (m, 1H), 8.15 (m, 1H), 7.96 (m, 1H), 7.82 (m, 2H), 7.75 - 7.69 (m, 4H), 7.68 - 7.61 (m, 10H), 7.60 - 7.55 (m, 3H), 7.54 - 7.47 (m, 11H), 7.46 - 7.40 (m, 2H), 7.31 (m, 1H).

[0111] Step two: Purification process of compound PO4:

[0112] (1) Chemical treatment process: The crude product obtained from column chromatography was dissolved in dichloromethane (100 mL), and aqueous hydrogen peroxide (1 eq.) and ethanol (5 mL) were added with stirring at room temperature. Subsequently, aqueous sodium hydroxide (3 eq. 3 M) was added, and stirring was continued. The reaction was stopped when TLC indicated the absence of boronate starting material. Aqueous sodium bisulfite was added to quench the excess hydrogen peroxide. The organic layer was collected by extraction with dichloromethane and back-extraction with water. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography using a mixture of dichloromethane and ethanol (100:1 v / v) as eluent to give a white solid. The product obtained from column chromatography was dissolved in dichloromethane, and isopropanol was added to precipitate the solid. The mixture was then heated and stirred under reflux for 12 h, filtered while hot, and the filter cake was dried.

[0113] The column chromatography separation was achieved by using dichloromethane:ethanol (100:1 v / v) as the eluent, the Rf value of 3-(diphenylphosphinyl)phenol was about 0.05, and the Rf value of PO2 was about 0.25.

[0114] (2) Sublimation purification. The obtained filter cake was subjected to gradient temperature sublimation to obtain the product. The HPLC purity of PO4 was 99.97% (HPLC detection). Figure 9

[0115] Example 5

[0116] The specific synthesis steps of the compound PO5 described in this Example 5 are as follows:

[0117] Step one: preparation of (2-bromo-9,9'-spirobifluorene-7-yl)diphenylphosphine oxide (compound 3)

[0118]

[0119] To a solution of (2-bromo-9,9'-spirobifluorene-7-yl)diphenylphosphine (4.86 g, 8.4 mmol) in dichloromethane (60 mL) was added hydrogen peroxide (15 mL) and ethanol (15 mL). The reaction was stirred at room temperature overnight. After the reaction was completed, an aqueous sodium sulfite solution was poured into the reaction mixture to reduce excess hydrogen peroxide. Then, the organic layer was first extracted with dichloromethane and then back-extracted with water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure and column chromatography separation was performed with dichloromethane and ethanol as the eluent to obtain a white solid with a yield of 97% (4.85 g).

[0120] 1 H NMR (400 MHz, CD2Cl2) δ 7.89 (dd, J = 10.1, 2.2 Hz, 1H), 7.85 (d, J = 7.6 Hz, 2H), 7.79 (d, J = 8.2 Hz, 1H), 7.55-7.48 (m, 8H), 7.42-7.36 (m, 6H), 7.19 (d, J = 11.48 Hz, 1H), 7.14 (dd, J = 8.2, 7.6 Hz, 2H), 6.86 (d, J = 1.8 Hz, 1H), 6.71 (d, J = 5.5 Hz, 2H).

[0121] Step two: preparation of diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9'- spirobifluorene-7-yl)phosphine oxide (compound 4)

[0122]

[0123] ​To the reaction mixture of Step one, [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium (37 mg, 0.05 mmol) was added under N2atmosphere, 2-bromo-9,9'-spirobifluorene-7-yl)diphenylphosphine oxide (3 g, 5.05 mmol), bis(pinacolato)diboron (1.54 g, 6.06 mmol), potassium acetate (1.48 g, 15.15 mmol), 1,4-dioxane (100 mL) and heated to 80 °C. After 12 h, the reaction mixture was cooled to room temperature, the solvent was evaporated under reduced pressure and extracted with dichloromethane and water. The collected organic layer was back extracted with water, dried over anhydrous magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography using dichloromethane and ethanol mixture as eluent to obtain white solid with 83.56% yield (2.71 g).

[0124] 1 H NMR (500 MHz, CD2Cl2) δ 7.95-7.92 (m, 2H), 7.87 (d, J = 7.7 Hz, 2H), 7.53 (dd, J = 7.7, 0.9 Hz, 1H), 7.53-7.47 (m, 7H), 7.42-7.37 (m, 6H), 7.20 (d, J = 11.7 Hz, 1H), 7.14 (m, 2H), 7.06 (s, 1H), 6.69 (d, J = 7.6 Hz, 2H), 1.23 (s, 12H).

[0125] Step three: Preparation of compound PO5

[0126]

[0127] Palladium acetate (0.036, 8 mg), tricyclohexylphosphine (0.14 mmol, 39 mg) were added to a reaction mixture of diphenyl(2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-9,9'- spirobifluorene-7-yl)oxidediphenyl(2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-9,9'- spirobifluorene-7-yl)oxide (2.5 g, 3.89 mmol), 3-bromo-l,10-phenanthroline (1 g, 3.54 mmol), aqueous sodium carbonate (2 M, 23.6 mmol), toluene (200 mL), ethanol (50 mL) under N2atmosphere. The reaction was heated to 90 °C and stirred overnight. After cooling to room temperature, water was added, the organic layer was separated and back-extracted with water. The resulting organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent was evaporated under reduced pressure and column chromatography was performed using a gradient of dichloromethane and ethanol mixtures (100:1 v / v) (to remove residual diphenyl(2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-9,9'- spirobifluorene-7-yl)oxide), dichloromethane and ethanol mixtures (50:1 v / v) (to remove residual 3-bromo-l,10-phenanthroline), dichloromethane and ethanol mixtures (20:1 v / v). For the samples isolated by column chromatography, further purification was performed using ethyl acetate and alcoholic solvents to give a white solid (1.12 g, 42%).

[0128] 1 H NMR (500 MHz, Methylene Chloride-d2 Figure 10 ) δ 9.29 (d, J = 2.3 Hz, 1H), 9.14 (dd, J = 4.3, 1.7 Hz, 1H), 8.28 (dd, J = 8.9, 2.3 Hz, 2H), 8.15 (d, J = 7.95 Hz, 1H), 8.03 (dd, J = 7.8, 2.5 Hz, 1H), 7.96 - 7.92 (m, 3H), 7.81 (dd, J = 15.3, 8.9 Hz, 2H), 7.65 (dd, J = 8.1, 4.3 Hz, 1H), 7.59 - 7.54 (m, 7H), 7.47 - 7.42 (m, 6H), 7.28 (d, J = 11.6 Hz, 1H), 7.23 - 7.19 (m, 3H), 6.84 (d, J = 7.7 Hz, 2H).

[0129] Step four: purification process of compound PO5

[0130] (1) Chemical treatment process: The crude product from step three column chromatography was dissolved in dichloromethane (100 mL), and hydrogen peroxide aqueous solution (1 eq.) and ethanol (5 mL) were added, and stirred at room temperature. Subsequently, sodium hydroxide aqueous solution (3 eq. 3M) was added. After stirring for 30 min, sodium bisulfite aqueous solution was added to quench the excess hydrogen peroxide. Subsequently, dichloromethane was used to extract, and the organic layer was collected and back-extracted with water; the obtained organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure and separated by column chromatography, using dichloromethane and ethanol mixture (50:1 v / v) and dichloromethane and ethanol mixture (20:1 v / v) as eluent, respectively, to obtain a white solid.

[0131] Using dichloromethane: ethanol (100:1 v / v) as the developing agent, the Rf value of 3-(diphenylphosphinyl)phenol was 0.05, while PO5 was essentially at the origin; when the ratio of dichloromethane: ethanol was increased to 20:1 v / v, the Rf value of 3-(diphenylphosphinyl)phenol was 0.8, while the Rf value of PO5 was 0.2. The polarity of 3-(diphenylphosphinyl)phenol should be similar to that of 7-(diphenylphosphinyl)-(9,9'-spirobifluorene)-2-ol, so that column chromatography separation can be achieved.

[0132] (2) Sublimation purification. The obtained filter cake was subjected to gradient temperature sublimation to obtain the product. HPLC detection showed that the HPLC purity of PO5 was 99.96% ( Figure 11 ).

[0133] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited by the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, and are all included in the protection scope of the present application.

Claims

1. A method for preparing a class of high-purity aromatic phosphine oxides, characterized in that, The preparation method is as follows: Where X is Cl, Br, or I; m = 1-2; when m = 2, R1 may be the same or different; the polarity of Br-R2 is less than that of aromatic phosphine oxides; R1 can be any of the following structures: R3 and R4 are alkyl, aryl, or heteroaryl groups; R2 can be any of the following structures: R5 is an aryl or heteroaryl group; The oxidant in step (1) is hydrogen peroxide; In step (5), the oxidant is at least one of hydrogen peroxide, sodium peroxide, potassium peroxide, di-tert-butyl peroxide, peracetic acid, and benzoyl peroxide.

2. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 1, characterized in that, Includes the following steps: (1) Diphenyl(monobromoaryl)phosphine The raw material was oxidized with hydrogen peroxide to obtain diphenyl (monobromoaryl)phosphine oxide. (2) The diphenyl (monobromoaryl) phosphine oxide obtained in step (1) Palladium-catalyzed borate esterification yields diphenylarylphosphine oxide borate ester. (3) The diphenylarylphosphine oxide borate obtained in step (2) Aromatic phosphine oxides were obtained by Suzuki coupling reaction with the bromoaryl derivative Br-R2. Crude products; (4) For the aromatic phosphine oxides obtained in step (3) The crude product was separated by rapid column chromatography to remove Br-R2; (5) Dissolve the crude product of aromatic phosphine oxides obtained in step (4) with Br-R2 removed in an organic solvent, add an oxidant and an alkali, so that the residual aromatic phosphine oxide borate esters and their boric acid derivatives are converted into the corresponding phenolic derivatives. (6) Further post-processing, including column chromatography, solvent washing, recrystallization and sublimation, is used to obtain high-purity aromatic phosphine oxides.

3. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 2, characterized in that: The molar ratio of diphenyl (monobromoaryl)phosphine to hydrogen peroxide in step (1) is 1:3 to 6.

4. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 2, characterized in that: In step (2), diphenyl (monobromoaryl)phosphine oxide is mixed with palladium catalyst and pinacol diboron ester and then subjected to Suzuki coupling reaction; The molar ratio of the diphenyl (monobromoaryl)phosphine oxide to the palladium catalyst and pinacol diboron ester is 1:0.01-0.03:1-3.

5. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 2, characterized in that: The molar ratio of diphenylaryl phosphine oxide ester to bromoaryl derivative Br-R2 in step (3) is 1:1 to 1.3; The temperature of the Suzuki coupling reaction in step (3) is 70-100°C and the reaction time is 1-24h.

6. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 2, characterized in that: The eluent used in the column chromatography described in step (4) is dichloromethane or a mixture of dichloromethane and ethanol.

7. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 2, characterized in that: The specific process in step (5) is as follows: the coupling product after removing Br-R2 is dissolved in an organic solvent, then an oxidant is added and stirred, followed by an alkaline solution and stirred. The organic solvent mentioned in step (5) is a mixed solvent of dichloromethane and alcohol, wherein the alcohol is at least one of ethanol, methanol and isopropanol.

8. A method for preparing a class of high-purity aromatic phosphine oxides according to claim 2 or 7, characterized in that: The molar ratio of the crude product of the aromatic phosphine oxides to the oxidant in step (5) is 1:1 to 20. The molar ratio of oxidant to alkali in step (5) is 1:1 to 20.

9. A method for preparing a class of high-purity aromatic phosphine oxides according to claim 2 or 7, characterized in that: The alkali used in step (5) is at least one of sodium hydroxide and potassium hydroxide.

10. The method for preparing a class of high-purity aromatic phosphine oxides according to claim 2, characterized in that: The eluent used in the column chromatography described in step (6) is a mixed solvent of dichloromethane and ethanol; The sublimation described in step (6) is a purification process using gradient temperature sublimation.

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