Preparation method of diphenylphosphine oxide compound and diphenylphosphine oxide compound

Abstract

The present invention relates to the field of compound preparation, and more particularly to a method for preparing diphenylphosphine oxide compounds and diphenylphosphine oxide compounds. The method uses an electron-rich aromatic compound as a starting material, and in the presence of PCl3 and a Lewis acid catalyst, a one-step reaction produces the diphenylphosphine oxide compound, which can then be obtained through simple post-processing to obtain a high-purity product. According to the present invention, the diphenylphosphine oxide compound can be obtained simply and efficiently. Compared to conventional methods, this method has relatively readily available raw materials, high atom economy, simple post-processing, and a high-purity product.

Description

Technical Field

[0001] The present invention relates to fine chemical synthesis, and in particular to a method for preparing a diphenylphosphine oxide compound and the diphenylphosphine oxide compound prepared thereby. Background Art

[0002] Organophosphorus compounds are a class of compounds consisting of phosphorus (P) atoms directly linked to carbon (C) atoms. These compounds exhibit diverse structures and chemical properties, primarily because the electronic configuration of the phosphorus atom allows them to form a variety of chemical bonds and structures. They have broad applications in agriculture, pharmaceuticals, chemicals, energy, and other fields. Diphenylphosphine oxides, in particular, serve as key intermediates for the preparation of diphosphorus ligand-based precious metal catalysts, coupling agents, and polymers or composite materials with specialized properties.

[0003] However, the conventional and widely used method for preparing diphenylphosphine oxide compounds primarily uses aromatic halides as raw materials, which are first reacted with magnesium powder to prepare a Grignard reagent, and then reacted with diethyl phosphite to obtain the product. In this method, the resulting reaction solution must undergo extraction, concentration, and column chromatography to obtain the product. This type of reaction not only requires high anhydrous conditions and complex operations, but also requires purification using chromatographic methods such as column chromatography, which greatly increases cost and time consumption. Summary of the Invention

[0004] In light of the aforementioned problems in the prior art, the present invention creatively discovered that by using a relatively electron-rich aromatic compound as the starting substrate, employing a sufficient excess of PCl3 as the reactant to react with the substrate and also serving as the reaction medium, and adding a Lewis acid catalyst to the reaction, diphenylphosphine oxide compounds can be obtained in a single step. Furthermore, this preparation method is simple to operate and produces high-purity products, better meeting the requirements of high atom economy, environmental friendliness, and strong operability in organic synthesis, and can also be applied in industrial production.

[0005] Specifically, the gist of the present invention is as follows.

[0006] [1] A method for preparing a diphenylphosphine oxide compound, characterized by comprising:

[0007] (1) a reactant mixing step, which comprises adding a substrate and phosphorus trichloride into a reaction vessel, and stirring until the substrate is dissolved, wherein the substrate is a benzene compound with or without a substituent, and the volume of phosphorus trichloride added in mL is 3 to 10 times the mass of the substrate in g.

[0008] (2) A catalytic reaction step, which comprises adding a Lewis acid catalyst in batches to the solution obtained in step (1) and performing the reaction at a reaction temperature of 40 to 80°C.

[0009] [2] The preparation method according to [1] further comprises:

[0010] (3) a product separation step, which comprises evaporating and recovering phosphorus trichloride after the reaction in step (2), slowly adding a water-soluble aprotic organic solvent to the evaporated concentrate, stirring, and then adding the concentrate to an alkaline aqueous solution, stirring and crystallizing to obtain the product.

[0011] [3] The preparation method according to [2] further comprises:

[0012] (4) Product purification step, which is to add a good solvent to the product obtained in step (3) and stir, filter to remove insoluble matter, and concentrate the filtrate under reduced pressure to 1 / 5 to 1 / 2 of the original volume, then slowly add a poor solvent until a large amount of solid precipitates, stir, filter and dry the solid.

[0013] [4] The preparation method according to any one of [1] to [3], wherein the substrate has a structure represented by the following formula (a):

[0014]

[0015] In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms, and R1 and R2 may be bonded to each other to form a ring.

[0016] R3 represents a substituent, there may be more than one R3 or no R3. When R3 is present, it is not located at the para position of the NR1R2 structure.

[0017] [5] The production method according to any one of [1] to [3], wherein in the reactant mixing step (1),

[0018] During the stirring, the internal temperature of the reaction vessel was maintained at -20 to 20°C by cooling means.

[0019] [6] The preparation method according to any one of [1] to [3], wherein in the catalytic reaction step (2),

[0020] The Lewis acid catalyst is one or more selected from aluminum trichloride, boron trifluoride, ferric trichloride, and tin tetrachloride.

[0021] The molar equivalent of the Lewis acid is 1.0 to 5.0 equivalents relative to the substrate.

[0022] [7] The preparation method according to [6], in the catalytic reaction step (2),

[0023] The molar equivalent of the Lewis acid is 1.0 to 2.0 equivalents relative to the substrate.

[0024] [8] The preparation method according to any one of [1] to [3], wherein in the catalytic reaction step (2),

[0025] The reaction temperature is 65-80°C.

[0026] [9] The production method according to any one of [1] to [3], wherein in the catalytic reaction step (2),

[0027] The reaction is carried out under the reflux condition of phosphorus trichloride.

[0028]

[10] The preparation method according to [2], in the product separation step (3),

[0029] The water-soluble aprotic organic solvent is one or more selected from acetonitrile, ethylene glycol dimethyl ether, acetone, DMSO, DMF, DMAc, and NMP.

[0030] The amount of the water-soluble aprotic organic solvent added in mL is 3 to 10 times the mass of the substrate in g.

[0031]

[11] The preparation method according to [2], in the product separation step (3),

[0032] The alkaline aqueous solution is an aqueous solution of alkali metal hydroxide, and the concentration of the alkali metal hydroxide is 5% to 50% by mass.

[0033]

[12] According to the preparation method described in [2], in the product separation step (3),

[0034] The method of adding to the alkaline aqueous solution is dropwise addition.

[0035]

[13] According to the preparation method described in [3], in the product purification step (4),

[0036] The good solvent is one or more selected from dichloromethane, ethyl acetate, dichloroethane, methyl tert-butyl ether, and ethylene glycol dimethyl ether.

[0037] The poor solvent is at least one selected from n-hexane, n-heptane, n-pentane, and petroleum ether.

[0038]

[14] The preparation method according to [4],

[0039] The substrate does not have R3, or R3 is an alkyl group having 1, 2 or 3 carbon atoms.

[0040]

[15] The preparation method according to [4],

[0041] The prepared diphenylphosphine oxide compound has the structure shown in the following formula (b):

[0042]

[0043] In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms, and R1 and R2 may be bonded to each other to form a ring.

[0044] R3 represents a substituent, there may be more than one R3 or no R3. When R3 is present, it is not located at the para position of the NR1R2 structure.

[0045]

[16] The preparation method according to any one of [1] to [3],

[0046] The substrate is one of the following compounds,

[0047]

[0048] The Lewis acid catalyst is aluminum trichloride.

[0049]

[17] A diphenylphosphine oxide compound, characterized in that it is prepared by the method described in any one of [1] to

[16] .

[0050]

[18] A diphenylphosphine oxide compound, characterized in that it has a structure represented by the following formula (b):

[0051]

[0052] In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms, and R1 and R2 may be bonded to each other to form a ring.

[0053] R3 represents a substituent, there may be more than one R3 or no R3. When R3 is present, it is not located at the para position of the NR1R2 structure.

[0054]

[19] A diphenylphosphine oxide compound, characterized in that it is one of the following compounds,

[0055]

[0056] An example of the preparation method of the diphenylphosphine oxide compound of the present invention can be shown in the following formula.

[0057]

[0058] R1or R2=-CH3,-CH2CH3n-Pr,i-Pr,n-Bu,t-Bu

[0059] R3=-H,-CH3,-CH2CH3,-CH2CH2CH3

[0060] Lewis acid=AlCl3, BF3, SnCl4 or FeCl3

[0061] R3 represents a single or multiple substitution except for the para position of the amino group

[0062] The preparation method of the diphenylphosphine oxide compound of the present invention has the following significant advantages.

[0063] (1) The reaction reagents and solvents used in the synthesis process are all commonly used industrial products and are relatively cheap, thus reducing the synthesis cost.

[0064] (2) The reaction steps are simple and the reaction conditions are mild. The synthesis process of the present invention adopts a one-step reaction preparation, and the reaction temperature is relatively low, so the required synthesis equipment is simple and meets industrial requirements.

[0065] (3) The product is highly pure and can be easily separated. For example, in one embodiment, the crude product obtained from the reaction of the present invention has a relatively high purity. After the recrystallization step in step (4), the product purity can be as high as 98% or more. Due to the high purity of the product, no special separation and purification treatment is required after the reaction, thereby improving product quality and reducing costs.

[0066] (4) Environmentally friendly and high atom economy. In the preparation method of the present invention, phosphorus trichloride is relatively excessive, which can ensure that the starting substrate aromatic compound is fully reacted. At the same time, phosphorus trichloride can be recovered by evaporation and reused in the reaction. Therefore, while the atom economy is extremely high, the impact on the environment is reduced.

[0067] Furthermore, the product obtained by the preparation method of the diphenylphosphine oxide compound of the present invention can be used as a monomer for preparing diphosphorus ligand noble metal catalysts (such as BINAP), and may be further applied to various asymmetric synthesis reactions, including asymmetric reduction reactions, asymmetric isomerization reactions, asymmetric hydrosilylation, etc.; in addition, the hydrogen in the product obtained by the present invention can be further introduced into other functional groups through a one-step reaction to prepare triarylphosphine oxide compounds, which can be used as the main ligand of homogeneous catalysts and are widely used in the preparation of medicines, dyes and additives. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Figure 1 This is the liquid chromatography-mass spectrometry LCMS characterization result of the diphenylphosphine oxide compound prepared in Example 1.

[0069] Figure 2 is the nuclear magnetic resonance proton of the diphenylphosphine oxide compound prepared in Example 1 1 Characterization results of HNMR. DETAILED DESCRIPTION

[0070] The present invention relates to a method for preparing a diphenylphosphine oxide compound, which is characterized by comprising: (1) a reactant mixing step, which comprises adding a substrate and phosphorus trichloride into a reaction vessel and stirring until the substrate is dissolved, wherein the substrate is a benzene compound with or without a substituent, and the volume of the added phosphorus trichloride in mL is 3 to 10 times the mass of the substrate in g; and (2) a catalytic reaction step, which comprises adding a Lewis acid catalyst in batches to the solution obtained in step (1) and carrying out the reaction at a reaction temperature of 40 to 80°C.

[0071] In one embodiment, the preparation method of the above-mentioned diphenylphosphine oxide compound further comprises:

[0072] (3) a product separation step, which comprises evaporating and recovering phosphorus trichloride after the reaction in step (2), slowly adding a water-soluble aprotic organic solvent to the evaporated concentrate, stirring, and then adding the concentrate to an alkaline aqueous solution, stirring and crystallizing to obtain the product.

[0073] In one embodiment, the preparation method of the above-mentioned diphenylphosphine oxide compound further comprises:

[0074] (4) Product purification step, which is to add a good solvent to the product obtained in step (3) and stir, filter to remove insoluble matter, and concentrate the filtrate under reduced pressure to 1 / 5 to 1 / 2 of the original volume, then slowly add a poor solvent until a large amount of solid precipitates, stir, filter, and dry the solid.

[0075] <Reactant Mixing Step>

[0076] In the reactant mixing step (1) of the present invention, a substrate and phosphorus trichloride are added to a reaction vessel and stirred until the substrate is dissolved. The substrate is a benzene compound with or without a substituent, and the amount of phosphorus trichloride added is 3 to 10 times (v / m) of the substrate, that is, the value in mL is 3 to 10 times the value of the mass of the substrate in g.

[0077] A feature of the present invention is to add a sufficient excess of phosphorus trichloride relative to the reaction substrate. Traditionally in similar synthetic preparations, common experimental designs are to add approximately equimolar reactants, or to make the starting substrate excessive. In the present invention, the inventors have found that surprisingly by adding a sufficient excess of phosphorus trichloride, phosphorus trichloride simultaneously acts as a participating reactant and reaction medium, obtaining an extremely excellent synthesis effect. Its specific mechanism is still unclear, but it is speculated that phosphorus trichloride undergoes electrophilic substitution at the para position of N in the presence of Lewis acid, slowly generating an intermediate substituted by phosphorus dichloride, which has higher electrophilic substitution activity than phosphorus trichloride and can quickly undergo electrophilic substitution reaction with the substrate in the system to generate diphenylphosphine chloride compounds, which are hydrolyzed to the target product under the action of water. Excessive addition of phosphorus trichloride can effectively promote the reaction and prevent other derivatives formed by the substrate from being mixed into the product as by-products, thereby ensuring the purity of the product. On the other hand, the substrate can be fully dissolved in phosphorus trichloride, ensuring that the reaction system is uniform and stable and the reactants are fully contacted. Phosphorus trichloride is electrophilic and has the properties of a Lewis acid. Using phosphorus trichloride as a reaction medium greatly improves the reaction efficiency.

[0078] To fully achieve the above-mentioned effects, the amount of phosphorus trichloride used is 3 to 10 times (v / m) of the substrate. By adding an amount above the lower limit, it is ensured that the phosphorus trichloride is sufficiently excessive to act as a reaction medium. If the phosphorus trichloride addition amount is too low, the raw materials and products have poor solubility, the system is very viscous, and a full reaction cannot be guaranteed. By adding an amount below the upper limit, the reaction efficiency can be improved and other side reactions can be avoided. For example, a large amount of phosphorus dichloride-substituted intermediates may be generated, which may generate monosubstituted phosphorous acid byproducts after hydrolysis, resulting in a reduced product yield.

[0079] The starting substrate of the present invention is a benzene compound with or without a substituent. In one embodiment, to ensure the reaction proceeds, the benzene compound is a relatively electron-rich benzene compound. Here, relatively electron-rich means that the electron density in the benzene ring of the benzene compound is not less than the electron density of the compound benzene, that is, generally means that the benzene ring is not substituted with an electron-withdrawing group.

[0080] In one embodiment, preferably, the substrate has a structure shown in the following formula (a):

[0081]

[0082] In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms. The alkyl group referred to in the present invention includes possible isomers, that is, the alkyl group having 3 carbon atoms includes propyl, isopropyl, cyclopropyl, etc., and the alkyl group having 4 carbon atoms includes n-butyl, sec-butyl, tert-butyl, cyclobutyl, etc. R1 and R2 can be bonded to each other to form a ring,

[0083] R3 represents a substituent. There may be more than one R3 or no R3. When R3 is present, all R3s are not located in the para position of the NR1R2 structure. Preferably, the chemical and physical properties of R3 do not substantially affect the reaction, and R3 is preferably an alkyl group having 1, 2, or 3 carbon atoms. Since the two substrate molecules are linked by the phosphine oxide structure at the para position of the NR1R2 structure, R3 is not located in the para position of the NR1R2 structure.

[0084] The obtained diphenylphosphine oxide compound has an amino structure when the substrate has the above structure, and can be widely used in industry as a ligand in fine chemicals.

[0085] In the preparation method of the present invention, during stirring, cooling measures are used to maintain the internal temperature of the reaction vessel at -20 to 20°C. By pre-mixing the substrate and phosphorus trichloride at low temperature, the substrate can be fully dissolved and evenly mixed in the phosphorus trichloride. During the actual dissolution, a completely clear, impurity-free, stable reactant mixture is obtained, which facilitates the smooth progress of the reaction. Furthermore, as described below, pre-mixing the reactants and adding the catalyst in batches to the mixed reactant mixture further improves reaction efficiency.

[0086] <Catalytic Reaction Step>

[0087] In the catalytic reaction step (2) of the present invention, a Lewis acid catalyst is added portionwise to the dissolved solution obtained in step (1), and the reaction is carried out at a reaction temperature of 40 to 80°C.

[0088] In the present invention, by premixing the reactants and adding the Lewis acid catalyst in batches to the uniform and stable reactant mixture, the reaction can be ensured to proceed in a substantially homogeneous state within the entire reaction system, ensuring efficient reaction performance while reducing the occurrence of side reactions due to uneven mixing. Furthermore, as described above, phosphorus trichloride generates a phosphorus dichloride-substituted intermediate in the presence of the Lewis acid. This intermediate undergoes an electrophilic substitution reaction with the substrate in the system to generate a diphenylphosphine chloride compound. The batchwise addition of aluminum trichloride can further ensure the generation of the diphenylphosphine chloride compound. If the Lewis acid is added all at once, due to the excess amount, the substrate may be completely converted into the phosphorus dichloride-substituted intermediate, preventing further reaction.

[0089] Here, the batch addition is performed using a batch addition method known in the field of organic synthesis. In one example, the Lewis acid solid can be divided into several portions, such as 3 to 10 portions, and added at regular intervals to ensure that the catalyst added each time is evenly mixed.

[0090] The Lewis acid catalyst may be a common Lewis acid catalyst in the art, such as a transition metal salt Lewis acid catalyst. In one embodiment, the Lewis acid catalyst is preferably selected from one or more of aluminum trichloride, boron trifluoride, ferric trichloride, and tin tetrachloride. From the perspective of ease of industrial implementation, aluminum trichloride is more preferred.

[0091] In one embodiment, the molar equivalent of the Lewis acid is 1.0 to 5.0 equivalents relative to the starting substrate, preferably 1.0 to 2.0 equivalents, more preferably 1.0 to 1.5 equivalents. By adding an amount greater than the lower limit, the reaction can be effectively catalyzed, while by adding an amount less than the upper limit, excessive addition can be avoided, which can lead to saturation of the catalytic effect and adverse effects on synthesis and economy.

[0092] The above reaction is carried out at a reaction temperature of 40 to 80° C., preferably 65 to 80° C., more preferably 70 to 78° C. In one embodiment, the reaction is carried out while refluxing the phosphorus trichloride. By keeping the reaction temperature above the above lower limit, the reaction rate can be effectively increased, and by keeping the reaction temperature below the above upper limit, the stability of the reaction system can be increased, unnecessary side reactions can be avoided, and the reaction conditions are mild, which is suitable for industrial application.

[0093] The reaction time of the above reaction is not particularly limited. The time point of completion of the reaction can be determined by a determination method known in the art, and the reaction can be terminated and subsequent separation and purification can be performed.

[0094] <Product Separation Step>

[0095] In the product separation step (3) of the present invention, after the reaction in step (2) is completed, phosphorus trichloride is evaporated and recovered, and a water-soluble aprotic organic solvent is slowly added to the evaporated concentrate. After stirring, the concentrate is added to an alkaline aqueous solution and stirred for crystallization to obtain a preliminary crude product.

[0096] After the reaction is completed in the preparation method of the present invention, phosphorus trichloride can be evaporated and recovered. The evaporation can be carried out by known means and conditions. The specific evaporation temperature can be appropriately selected. If necessary, means known in the art such as reduced pressure can also be used.

[0097] In one embodiment, the water-soluble aprotic organic solvent is one or more selected from acetonitrile, ethylene glycol dimethyl ether, acetone, DMSO, DMF, DMAc, and NMP. For example, acetonitrile may be used in consideration of cost. Here, a water-soluble aprotic organic solvent is used to facilitate post-treatment by adding water for miscibility and precipitation of the product.

[0098] In one embodiment, the amount of the water-soluble aprotic organic solvent added in mL is 3 to 10 times the mass of the substrate in g.

[0099] The present invention precipitates a preliminary crude product in an alkaline aqueous solution. In particular, when the substrate is an amino-containing compound represented by formula (a), a good precipitation effect can be achieved in an alkaline aqueous solution. In one embodiment, the alkaline aqueous solution is an aqueous solution of an alkali metal hydroxide, and the concentration of the alkali metal hydroxide is 5% to 50% by mass. In one embodiment, the concentrate is added to the alkaline aqueous solution dropwise, thereby achieving a good precipitation effect.

[0100] The above-mentioned product separation process does not rely on specific equipment and can be completed by conventional organic synthesis equipment and instruments, and has mild conditions, short time consumption and high separation efficiency.

[0101] <Product Purification Step>

[0102] In the product purification step (4) of the present invention, the product can be purified by conventional means known in the art. Considering cost and convenience, recrystallization can be used for purification. Specifically, the product obtained in step (3) can be added to a good solvent and stirred, and the insoluble matter can be removed by filtration. The filtrate can be concentrated under reduced pressure to 1 / 5 to 1 / 2 of the original volume, and then a poor solvent can be slowly added until a large amount of solid precipitates. The product can be stirred, filtered, and dried.

[0103] In one embodiment, the good solvent is one or more selected from dichloromethane, ethyl acetate, dichloroethane, methyl tert-butyl ether, and ethylene glycol dimethyl ether. In one embodiment, the poor solvent is one or more selected from n-hexane, n-heptane, n-pentane, and petroleum ether.

[0104] <Product>

[0105] The present invention also relates to a diphenylphosphine oxide compound, which is characterized in that it is prepared by the above method.

[0106] In one embodiment, the diphenylphosphine oxide compound prepared by the preparation method of the present invention has a structure shown in the following formula (b):

[0107]

[0108] In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms,

[0109] R3 represents a substituent, there may be more than one R3 or no R3. When R3 is present, it is not located at the para position of the NR1R2 structure.

[0110] In one embodiment, the substrate of the preparation method of the present invention is one of the following compounds,

[0111]

[0112] The diphenylphosphine oxide compound thus obtained is one of the following compounds,

[0113]

[0114] The embodiments of the present invention are described in detail below. It should be noted that the embodiments described below are exemplary and are only used to explain the present invention, and should not be understood as limiting the present invention.

[0115] Example 1

[0116]

[0117] Add 50.0g of N,N-dimethyl-m-toluidine and 200ml of phosphorus trichloride to a three-necked flask and cool the solution to 10-15°C while stirring until it is completely clear and dissolved. Then, add 51.4g of aluminum trichloride in six batches over 30 minutes while maintaining the temperature at 10-15°C. After addition, react at 75-77°C for 16 hours.

[0118] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 100 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 400 ml of ice-cold 15% sodium hydroxide solution (pH>12). The solution is stirred at room temperature for crystallization for 1 to 2 hours, filtered, washed with purified water, and dried to obtain 43.14 g of a crude solid product.

[0119] Add 43.14g of crude product and 250ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter with suction. The filtrate is concentrated to about 100ml, 300ml of n-heptane is added dropwise, stirred for 2h, filtered with suction, and the filter cake is washed with n-heptane and dried in a forced air drying oven at 45°C for 4h to obtain 26.5g of white powder solid with a purity of 98.78%. Liquid chromatography-mass spectrometry coupled with LCMS and nuclear magnetic resonance spectroscopy are used to analyze the product. 1 The structural characterization was performed by HNMR, confirming that the obtained product was the target product.

[0120] Example 2

[0121]

[0122] Add 65.7g of N,N-diisopropylaniline and 230ml of phosphorus trichloride to a three-necked flask and cool to 0-5°C while stirring until the solution is completely clear and dissolved. Then, add 51.4g of aluminum trichloride in six batches over 30 minutes while controlling the temperature at 10-15°C. React at 75-77°C for 12 hours.

[0123] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 120 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 450 ml of ice-cold 10% sodium hydroxide solution (pH>12). The mixture is stirred at room temperature for crystallization for 1 to 2 hours, filtered, washed with purified water, and dried to obtain 51.1 g of a crude solid product.

[0124] Add 51.1 g of the crude product and 300 ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter, concentrate the filtrate to about 100 ml, add 300 ml of n-heptane dropwise, stir for 2 h, filter, wash the filter cake with n-heptane, and dry in a forced air drying oven at 45 ° C for 4 h to obtain 32.3 g of an off-white solid with a purity of 98.62%.

[0125] Example 3

[0126]

[0127] Add 50.0g of N,N-dimethyl-m-toluidine and 400ml of phosphorus trichloride to a three-necked flask and cool to a temperature of 10-15°C while stirring until the solution is completely clear and dissolved. Then, add 51.4g of aluminum trichloride in six batches over 30 minutes while maintaining the temperature at 10-15°C. After addition, react at 75-77°C for 16 hours.

[0128] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 100 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 400 ml of ice-cold 15% sodium hydroxide solution (pH>12). The solution is stirred at room temperature for crystallization for 1 to 2 hours, filtered, washed with purified water, and dried to obtain 38.14 g of a crude solid product.

[0129] Add 38.14 g of the crude product and 250 ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter with suction. The filtrate is concentrated to about 100 ml, 300 ml of n-heptane is added dropwise, stirred for 2 h, filtered with suction, and the filter cake is washed with n-heptane. Dry in a forced air drying oven at 45 ° C for 4 h to obtain 18.5 g of a white powder solid with a purity of 98.12%.

[0130] Comparative Example 1

[0131]

[0132] Add 50.0g of N,N-dimethyl-m-toluidine and 32ml of phosphorus trichloride to a three-necked flask and cool to 10-15°C while stirring until the solution is completely clear and dissolved. Add 51.4g of aluminum trichloride in six batches over 30 minutes while maintaining the temperature at 10-15°C. The solution will be very viscous. After addition, react at 75-77°C for 16 hours.

[0133] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 100 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 400 ml of ice-cold 15% sodium hydroxide solution (pH>12). The solution is stirred at room temperature for 1 to 2 hours to allow crystallization. The solution is filtered, washed with purified water, and dried to obtain 21.54 g of a crude sticky solid.

[0134] Add 21.54 g of the crude product and 250 ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter with suction. The filtrate is concentrated to about 100 ml, 300 ml of n-heptane is added dropwise, stirred for 2 h, filtered with suction, and the filter cake is washed with n-heptane. Dry in a forced air drying oven at 45 ° C for 4 h to obtain 6.5 g of an off-white solid with a purity of 75.12%.

[0135] In Comparative Example 1, due to insufficient phosphorus trichloride content, the product amount was extremely small and the purity was extremely low.

[0136] Comparative Example 2

[0137]

[0138] Add 50.0g of N,N-dimethyl-m-toluidine and 600ml of phosphorus trichloride to a three-necked flask and cool the solution to 10-15°C while stirring until it is completely clear and dissolved. Then, add 51.4g of aluminum trichloride in six batches over 30 minutes while maintaining the temperature at 10-15°C. After addition, react at 75-77°C for 16 hours.

[0139] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 100 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 400 ml of ice-cold 15% sodium hydroxide solution (pH>12). The solution is stirred at room temperature for crystallization for 1 to 2 hours, filtered, washed with purified water, and dried to obtain 22.36 g of a crude solid product.

[0140] Add 22.36 g of the crude product and 250 ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter with suction. The filtrate obtained is concentrated to about 100 ml, 300 ml of n-heptane is added dropwise, stirred for 2 h, filtered with suction, and the filter cake is washed with n-heptane. Dry in a forced air drying oven at 45 ° C for 4 h to obtain 11.5 g of an off-white solid with a purity of 93.03%.

[0141] In Comparative Example 2, due to the excessively high phosphorus trichloride content, side reactions increased, the product amount was small, and the purity was low.

[0142] Comparative Example 3

[0143]

[0144] Add 50.0 g of N,N-dimethyl-m-toluidine and 200 ml of phosphorus trichloride to a three-necked flask, and then add 51.4 g of aluminum trichloride. Use the temperature control device as in Example 1, but the system is highly exothermic. After dissolution is complete, heat to 75-77°C and react for 16 hours.

[0145] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 100 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 400 ml of ice-cold 15% sodium hydroxide solution (pH>12). The solution is stirred at room temperature for crystallization for 1 to 2 hours, filtered, washed with purified water, and dried to obtain 12.36 g of a crude solid product.

[0146] Add 12.36 g of the crude product and 250 ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter with suction. The filtrate obtained is concentrated to about 100 ml, 300 ml of n-heptane is added dropwise, stirred for 2 h, filtered with suction, and the filter cake is washed with n-heptane. Dry in a forced air drying oven at 45 ° C for 4 h to obtain 4.2 g of an off-white solid with a purity of 88.56%.

[0147] In Comparative Example 3, since aluminum chloride was not added in batches, side reactions increased, the amount of product was very small, and the purity was low.

[0148] Example 4

[0149]

[0150] Add 50.0g of N,N-dimethyl-m-toluidine and 200ml of phosphorus trichloride to a three-necked flask and stir at room temperature until the solution is completely clear and dissolved. Then, add 51.4g of aluminum trichloride in six portions over 30 minutes at room temperature. This addition is highly exothermic. After complete addition, react at 75-77°C for 16 hours.

[0151] After the reaction is completed, phosphorus trichloride is recovered by evaporation. 100 ml of acetonitrile is added to the evaporated concentrate and stirred. The reaction solution is then added dropwise to 400 ml of ice-cold 15% sodium hydroxide solution (pH>12). The solution is stirred at room temperature for crystallization for 1 to 2 hours, filtered, washed with purified water, and dried to obtain 19.76 g of a crude solid product.

[0152] Add 19.76 g of the crude product and 250 ml of dichloromethane to a three-necked flask, stir and dissolve at room temperature, then filter with suction. The filtrate is concentrated to about 100 ml, 300 ml of n-heptane is added dropwise, stirred for 2 h, filtered with suction, and the filter cake is washed with n-heptane. Dry in a forced air drying oven at 45 ° C for 4 h to obtain 12.3 g of a white powder solid with a purity of 96.26%.

[0153] Industrial applicability

[0154] Compared with the existing technology, the present invention can efficiently complete the preparation of diphenylphosphine oxide compounds, with high reaction efficiency and high product purity. The compounds prepared by the present invention have great application value in the fields of precious metal catalysts, coupling agents, polymers with special properties or composite materials.

Claims

1. A method for preparing a diphenylphosphine oxide compound, characterized in that: include: (1) a reactant mixing step, which comprises adding a substrate and phosphorus trichloride into a reaction vessel and stirring until the substrate is dissolved, wherein the substrate has a structure represented by the following formula (a): In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms, and R1 and R2 may be bonded to each other to form a ring. R3 represents a substituent, there are more than one R3 or no R3, when R3 exists, it is not located in the para position of the NR1R2 structure, R3 is an alkyl group having 1, 2 or 3 carbon atoms, The volume of phosphorus trichloride added in mL is 3 to 10 times the mass of the substrate in g. (2) a catalytic reaction step, which comprises adding a Lewis acid catalyst in batches to the solution obtained in step (1), and carrying out the reaction at a reaction temperature of 40 to 80° C., wherein the Lewis acid catalyst is one or more selected from aluminum trichloride, boron trifluoride, ferric chloride, and tin tetrachloride, and the molar equivalent of the Lewis acid is 1.0 to 5.0 equivalents relative to the substrate. In the step (1) of mixing the reactants, the internal temperature of the reaction vessel is maintained at -20 to 20°C by cooling means during stirring. The prepared diphenylphosphine oxide compound has the structure shown in the following formula (b): In the formula, R1 or R2 are each independently an alkyl group having 1, 2, 3 or 4 carbon atoms, and R1 and R2 may be bonded to each other to form a ring. R3 represents a substituent, there are more than one R3 or no R3, when R3 exists, it is not located in the para position of the NR1R2 structure, R3 is an alkyl group having 1, 2 or 3 carbon atoms.

2. The preparation method according to claim 1, further comprising: (3) a product separation step, which comprises evaporating and recovering phosphorus trichloride after the reaction in step (2), slowly adding a water-soluble aprotic organic solvent to the evaporated concentrate, stirring, and then adding the concentrate to an alkaline aqueous solution, stirring and crystallizing to obtain the product.

3. The preparation method according to claim 2, further comprising: (4) Product purification step, which is to add a good solvent to the product obtained in step (3) and stir, filter to remove insoluble matter, and concentrate the filtrate under reduced pressure to 1 / 5 to 1 / 2 of the original volume, then slowly add a poor solvent until a large amount of solid precipitates, stir, filter and dry the solid.

4. The preparation method according to claim 1, wherein in the step (2) of catalytic reaction, The molar equivalent of the Lewis acid is 1.0 to 2.0 equivalents relative to the substrate.

5. The preparation method according to any one of claims 1 to 3, wherein in the step (2) of catalytic reaction, The reaction temperature is 65-80°C.

6. The preparation method according to any one of claims 1 to 3, wherein in the step (2) of catalytic reaction, The reaction is carried out under the reflux condition of phosphorus trichloride.

7. The preparation method according to claim 2, wherein in (3) the product separation step, The water-soluble aprotic organic solvent is one or more selected from acetonitrile, ethylene glycol dimethyl ether, acetone, DMSO, DMF, DMAc, and NMP. The amount of the water-soluble aprotic organic solvent added in mL is 3 to 10 times the mass of the substrate in g.

8. The preparation method according to claim 2, wherein in (3) the product separation step, The alkaline aqueous solution is an aqueous solution of alkali metal hydroxide, and the concentration of the alkali metal hydroxide is 5% to 50% by mass.

9. The preparation method according to claim 2, wherein in (3) the product separation step, The method of adding to the alkaline aqueous solution is dropwise addition.

10. The preparation method according to claim 3, wherein in (4) the product purification step, The good solvent is one or more selected from dichloromethane, ethyl acetate, dichloroethane, methyl tert-butyl ether, and ethylene glycol dimethyl ether. The poor solvent is at least one selected from n-hexane, n-heptane, n-pentane, and petroleum ether.

11. The preparation method according to any one of claims 1 to 3, The substrate is one of the following compounds, The Lewis acid catalyst is aluminum trichloride.

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