WO2022088569A1

WO2022088569A1 - Preparation method for bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide

Info

Publication number: WO2022088569A1
Application number: PCT/CN2021/078581
Authority: WO
Inventors: 赵国锋; 张齐; 毛桂红; 张建锋; 武瑞
Original assignee: 天津久日新材料股份有限公司
Priority date: 2020-10-29
Filing date: 2021-03-02
Publication date: 2022-05-05
Also published as: CN112159429A; CN112159429B

Abstract

A preparation method for bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide. In the preparation method, a specific ether compound is added as a complexing agent in the reaction of sodium sand and phenylphosphine dichloride. The addition of the complexing agent can effectively inhibit the formation of phenylphosphine sodium polyphosphide and promote the generation of phenylphosphine sodium, and no phenylphosphine hydrogen process is required, thereby reducing the process cost, and improving the safety of process procedures. In addition, since the complexing agent is a polar aprotic solvent, and is used in a small amount, the preparation method can reduce the content of organic matters in wastewater as compared with a conventional method of using a protic solvent as an activating agent or a proton source, and thus has certain environmental benefits and saves costs.

Description

A kind of preparation method of bis(2,4,6-trimethylbenzoyl) phenyl phosphine oxide

technical field

The invention belongs to the field of organic chemistry, and relates to a preparation method of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide.

Background technique

Acylphosphine oxide compounds are used as efficient photoinitiators for initiating the radiation polymerization of some unsaturated resins under UV light irradiation, especially for white formulations and glass fiber reinforced polyester/styrene systems and with light stabilizers Compatible with varnish systems and paint systems for outdoor use, such as for wood, paper, metal, plastic, optical fiber, as well as printing inks and pre-impregnated systems.

Among them, bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (initiator 819) and (2,4,6-trimethylbenzoyl)diphenylphosphine oxide (initiator TPO) Two of them are widely used and widely used.

In the prior art, the preparation method of bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide generally includes: first, reacting sodium metal and phenylphosphorus dichloride, adding a proton source (alcohols, amines, etc.) class) dissociation to obtain phenylphosphine hydrogen, phenylphosphine hydrogen reacts with 2.4.6-trimethylbenzoyl chloride under alkaline conditions, and finally oxidized to obtain the target product, the main problem of this process is: dissociation It requires more than 2 equivalents and cannot be recovered, resulting in a large amount of waste water containing organic matter, and there is phenylphosphine hydrogen in the reaction process, which is odorous and flammable, and there is a great potential safety hazard;

CN100436461C discloses a preparation method of acyl phosphine, the preparation method comprises: (1) reacting organophosphorus halide with metal sodium in the presence of an activator in a solvent, wherein the metal sodium is an alkali metal particle with an average particle size of ≤500 μm in the solvent exists in the form of a dispersion, (2) reacts with an acid halide subsequently; in this reaction, chlorobenzene and/or n-butanol are used as activators, but there is still the possibility of generating phenylphosphine hydrogen in the preparation process, which is not conducive to The safety of the reaction, at the same time, due to the presence of n-butanol, it will quickly react with the acyl halide to form an ester, increasing by-products and consuming the acyl halide, increasing the cost.

Therefore, it is very necessary to develop a preparation method of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide which has high operational safety and can avoid the generation of phenylphosphine hydrogen.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a preparation method of bis(2,4,6-trimethylbenzoyl) phenyl phosphine oxide. In the preparation method, the reaction between sodium sand and phenyl phosphine dichloride is added A specific ether compound is used as a complexing agent. The addition of the complexing agent can effectively inhibit the formation of sodium phenylphosphine polyphosphine, promote the formation of sodium phenylphosphine, and does not need to go through the phenylphosphine hydrogen process, which reduces the process cost. The safety of the process is improved; in addition, the above-mentioned complexing agent is a polar aprotic solvent, and the dosage is small. Compared with the traditional method using a protic solvent as an activator or a proton source, it can reduce the content of organic matter in wastewater , with certain environmental benefits and cost savings.

Sodium phenylphosphine polyphosphide refers to an intermediate containing 2 or more PP bonds or an intermediate sodium salt containing 2 or more PP bonds generated during the reaction, such as [P ₅ Ph ₅ ], [Na ₂ [P ₄ Ph ₄ ]] and other intermediates.

For this purpose, the present invention adopts the following technical solutions:

The invention provides a preparation method of bis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide, which comprises the following steps:

(1) mixing and reacting sodium sand, phenylphosphine dichloride and complexing agent in a non-polar solvent; wherein, the complexing agent is selected from cyclic ethers, ethers shown in formula 1) and those shown in formula 2). at least one of ethers;

Wherein, R ₁ , R ₂ and R ₃ are each independently selected from C1-C4 alkyl; n is selected from 1-20;

(2) in the reaction solution that step (1) obtains, add mes-trimethylbenzoyl chloride to react;

(3) subjecting the product of step (2) to oxidation reaction to obtain the bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide.

In the above-mentioned preparation method of the present invention, a complexing agent is added in the reaction between sodium sand and phenylphosphine dichloride, and the above-mentioned complexing agent belongs to a polar aprotic solvent, and in the reaction solution, it can react with the benzene generated by the reaction. Sodium phosphine forms a complex structure, which in turn inhibits the formation of clusters, so that the yield of the product sodium phenyl phosphine is significantly improved, the reaction rate with mesityl benzoyl chloride is accelerated, and the process of phenyl phosphine hydrogen is avoided. The safety is greatly improved; at the same time, the amount of the required complexing agent in the method of the present invention is small, thereby reducing the content of organic matter in the waste water; and the mes-trimethylbenzoyl chloride cannot be reacted in time or excessively reacted in the reaction process , will produce by-products such as mes-trimethyl benzoic anhydride and mes-trimethyl benzoate, reduce yield, increase raw material cost and purification cost at the same time; And the preparation method of the present invention adds the above-mentioned complex in the preparation process The mixture improves the reaction rate of sodium phenylphosphine intermediate and mes-trimethyl benzoyl chloride, avoids other side reactions from mes-trimethyl benzoyl chloride, and does not produce or less produces by-products, so the still residue of the preparation process The amount was also significantly reduced.

According to the research on the reaction process, the present invention finds that the action principle of the above-mentioned complexing agent in the reaction process of sodium sand and phenylphosphine dichloride can be inferred as follows, the complexing agent can well stabilize the sodium phenylphosphine produced , to generate a stable solvated sodium phenylphosphine. In the reaction step with acid chloride, it is mainly the rapid reaction of stable solvated sodium phenylphosphine and acid chloride to generate an acylphosphine compound. The reaction reduces the concentration of solvated sodium phenylphosphine and promotes More sodium phenylphosphine is generated to promote the continuous progress of the reaction. However, if the amount of the complexing agent is too large, the solubility of the sodium phenylphosphine intermediate in it will decrease, which is not conducive to the occurrence of the reaction. It is not easy to be exposed when it is wrapped inside, which is not conducive to the further reaction of P- ^and acid chloride in sodium phenylphosphine. The reaction is very slow, resulting in an incomplete reaction. If the reaction conditions are not strictly controlled, if there is water, mes-trimethyl will be formed quickly. Benzoic anhydride; and generally need washing in subsequent reaction steps and post-processing steps, unreacted acid chlorides will also produce a large amount of by-product acid anhydrides, resulting in low product yield and high cost; at the same time, the residual amount of metallic sodium is too large, and post-processing Danger. If the concentration of the complexing agent is too low or no complexing agent is added, the complexing agent cannot effectively form a complex with sodium phenylphosphine and exist stably, and will not produce or generate a small amount of mesityl benzoyl chloride. Intermediate; the addition of the above-mentioned complexing agent not only effectively inhibits the formation of polyphosphine of sodium phenylphosphine, but also promotes the forward reaction of the reaction, and further promotes the formation of sodium phenylphosphine.

The equation of the reaction scheme of the preparation method of the present invention is as follows:

In the above formula, x is the molar ratio of Na to phenylphosphine dichloride.

It can be seen from the above reaction equation that the addition of the complexing agent in the preparation method of the present invention increases the yield of the sodium phenylphosphine intermediate, thereby avoiding the reaction process of phenylphosphine hydrogen, the efficiency and safety of the reaction process. Sexually improved. The yield of the bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide prepared by the preparation method of the present invention can reach over 90%, and the purity can reach over 99.0%.

Preferably, in step (1), the molar ratio of phenylphosphine dichloride to complexing agent is 1:(0.01～2), for example, 1:0.05, 1:0.1, 1:0.2, 1:0.3, 1:0.4 , 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1 : 1.7, 1: 1.8, or 1: 1.9, etc., preferably 1: (0.2 to 1.0).

In the preparation method of the present invention, the addition amount of the complexing agent needs to be controlled within the above range. During the reaction of phenylphosphine dichloride and sodium sand, the complexing agent can effectively inhibit the mutual combination of P and P, and inhibit the The formation of polyphosphide of sodium phosphine promotes the formation of sodium phenylphosphine, and thus does not need to go through the phenylphosphine hydrogen process; when the amount of complexing agent added is too small, the improvement effect is not obvious; when the complexing agent is added When the amount is too large, the complex will affect the reaction rate, so that the negative ion center is completely wrapped in it and not easy to be exposed, which is not conducive to the further reaction of P- ^and acid chloride in the sodium phenylphosphine, and the reaction is very slow; at the same time, the amount of activator is too large, the intermediate The reduced solubility in the reaction system also leads to a slowing of the reaction rate.

Preferably, the cyclic ether is selected from tetrahydrofuran, 1,4-dioxane, 15-crown-5, 18-crown-6, 12-crown-4, dicyclohexane-18-crown- At least one of 6 and dibenzofuran, preferably 1,4-dioxane.

Preferably, the complexing agent is selected from

and / or

Preferably, the complexing agent is selected from anisole.

When the complexing agent of the present invention adopts the ether compound of the above-mentioned structure, its inhibition effect on the formation of sodium phenylphosphine polyphosphide is better.

Preferably, in step (1), the mass ratio of sodium sand to phenylphosphine dichloride is 1:(1-2.5), such as 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, or 1:2.4, etc., preferably 1:(1.7-2.2).

Preferably, in step (1), the mass ratio of sodium sand to the non-polar solvent is 1:5 to 15, such as 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13 or 1:14 etc.

In the preparation method of the present invention, the mass ratio of sodium sand to the non-polar solvent is within the above range, and the amount of solvent used is small, while ensuring a higher product yield, the process cost is significantly reduced, and the energy consumption is also significantly reduced.

Preferably, the non-polar solvent includes at least one of toluene, xylene and ethylbenzene.

Preferably, the method for mixing and reacting in step (1) comprises: in a reflux state, adding phenylphosphine dichloride to the sodium sand suspension to carry out the first reaction, then adding a complexing agent to carry out the second reaction .

Or, the method for mixing and reacting in step (1) includes: in a reflux state, adding phenylphosphine dichloride to the mixed solution of the sodium sand suspension and the complexing agent to carry out the reaction.

Through research, the present invention finds that by adopting the above two material mixing reaction methods, the complexing agent can effectively inhibit the formation of the polyphosphine intermediate of sodium phenylphosphine, and does not need to go through the phenylphosphine hydrogen process, which reduces the cost of the process. cost and improve the safety of the process.

The mixed solution of the sodium sand suspension and the complexing agent here refers to adding a complexing agent during the preparation process of the sodium sand suspension to form a mixed solution of the sodium sand suspension and the complexing agent.

Preferably, the preparation method of the sodium sand suspension includes: mixing sodium metal and a non-polar solvent, heating in an inert atmosphere, and crushing to obtain a sodium sand suspension.

Preferably, the heating temperature is 90-110°C, such as 90°C, 92°C, 95°C, 97°C, 100°C, 102°C, 105°C, 107°C, 110°C, and the like.

Preferably, the crushing method includes stirring; preferably a turbine mixer or a reaction mixing pump is used for stirring to reduce the average particle size of sodium and increase the contact area with phenylphosphine dichloride, thereby reducing the amount of sodium used.

Preferably, the inert atmosphere includes a nitrogen atmosphere.

Preferably, the method of adding phenylphosphine dichloride is dropwise addition.

Preferably, the time of the first reaction is 4-10h, for example, 5h, 6h, 7h, 8h or 9h and the like.

Preferably, the method of adding the complexing agent is dropwise addition.

Preferably, the time of the second reaction is 1-6h, such as 2h, 3h, 4h or 5h and the like.

Preferably, both the first reaction and the second reaction are carried out under the protection of an inert atmosphere.

Preferably, an alkaline substance is also added in step (1).

Preferably, the basic substance includes at least one of alkali metal hydroxides, oxides, alcohol compounds and carbonates; preferably alkali metal alcohol compounds.

Preferably, the alkali metal hydroxide is selected from sodium hydroxide.

Preferably, the alkali metal oxide is selected from potassium oxide.

Preferably, the alkali metal alcoholate is selected from the group consisting of sodium ethoxide, sodium methoxide, sodium butoxide, sodium tert-butoxide, sodium isopropoxide, potassium ethoxide, potassium methoxide, potassium butoxide, potassium tert-butoxide and isopropanol At least one of potassium, preferably sodium tert-butoxide.

Preferably, the alkali metal carbonate is selected from sodium carbonate and/or potassium carbonate.

Preferably, in step (1), the amount of alkaline substance added is 0.1-10% of the mass of phenylphosphine dichloride, for example, 0.5%, 1%, 2%, 3%, 4%, 5%, 6% %, 7%, 8%, or 9%, etc., preferably 1 to 5%.

According to the present invention, it is found through research that adding an alkaline substance in step (1) is beneficial to speed up the reaction rate and improve the production efficiency and production capacity. Compared with adding alkaline substance and adding no alkaline substance, adding alkaline substance can increase the reaction rate with sodium phenylphosphine and mesityl benzoyl chloride to 150-300%. In the step (1), the order of adding the alkaline substance may be before adding the complexing agent, or after the complexing agent is added, or may be added simultaneously with the complexing agent.

Preferably, the alkaline substance is added during the preparation of the sodium sand suspension. According to the research of the present invention, when the content of alcohols or metal salts of alcohols in the reaction system is too high, it will form a corresponding ester side reaction with mes-trimethylbenzoyl chloride, and the larger the amount thereof, the more the by-products will be. The present invention controls the added amount of alkoxide to be 0.1-10% of the mass of phenylphosphine dichloride, which can obviously improve the reaction rate while avoiding the occurrence of side reactions.

Preferably, the method of adding mes-trimethylbenzoyl chloride in step (2) is dropwise addition.

Preferably, the reaction temperature in step (2) is 60-100°C, such as 65°C, 70°C, 75°C, 80°C, 85°C, 90°C or 95°C, etc.

Preferably, the reaction time in step (2) is 4-10 h, such as 5 h, 6 h, 7 h, 8 h or 9 h, and the like.

Preferably, the reaction in step (2) is carried out under the protection of an inert atmosphere.

Preferably, in step (2), liquid separation is also included after the reaction is completed to obtain the first organic phase.

Preferably, the method for liquid separation is to add water to the solution after the reaction in step (2), and then stand for liquid separation to obtain the first organic phase.

Here, water is added to stand for liquid separation to obtain a first organic phase, wherein the first organic phase contains the reaction product of sodium phenylphosphine and mesityl benzoyl chloride, and the aqueous phase contains water and inorganic salts. An organic phase undergoes an oxidation reaction to prepare a product.

Preferably, the method of adding water is dropwise.

Preferably, the temperature of the liquid separation operation is less than 60°C, such as 20°C, 30°C, 40°C or 50°C, and the like.

Preferably, the method for the oxidation reaction in step (3) comprises adding hydrogen peroxide to the first organic phase to carry out the oxidation reaction.

Preferably, the hydrogen peroxide is added in the form of a hydrogen peroxide solution, preferably the concentration of the hydrogen peroxide solution is 20-50% (eg 20%, 25%, 30%, 35%, 40%, 45%, 50% %Wait).

Preferably, the temperature of the oxidation reaction is 30-60°C, such as 35°C, 40°C, 45°C, 50°C or 55°C, and the like.

Preferably, after the oxidation reaction, the method further comprises standing and liquid separation to obtain the second organic phase.

Preferably, the method further comprises adding alkaline solution to the second organic phase to carry out the reaction.

In the method of the present invention, alkali liquor is added to the second organic phase, which can neutralize the acid generated in the second organic phase, on the one hand, it can remove the organic by-products of acidic or alkali-sensitive impurities, and on the other hand The stratification of the organic phase and the aqueous phase can be promoted, thereby improving the yield and purity of the product.

Preferably, the alkali solution is added in an amount such that the pH value of the solution is 7-11, such as 7.5, 8, 8.5, 9, 9.5, 10, 10.5 and the like.

In the method of the present invention, it is preferable that the amount of alkali solution added makes the pH of the solution 7-11, which is more conducive to the improvement of subsequent recrystallization yield and purity.

Preferably, the solute of the lye is selected from at least one of sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium sulfite and sodium thiosulfate, preferably sodium carbonate.

Preferably, the lye solution is selected from sodium carbonate solution with a concentration of 3-8 wt % (eg, 4 wt %, 5 wt %, 6 wt % or 7 wt %, etc.).

Preferably, after adding the alkali solution, the temperature for the reaction is 50-60°C, for example, 52°C, 55°C, or 58°C.

Preferably, after adding the alkali solution, the reaction time is 0.5-3h, for example, 1h, 1.5h, 2h or 2.5h, etc.

Preferably, after adding the lye, and after the reaction is completed, it also includes standing for liquid separation to obtain the third organic phase.

Preferably, the method further comprises crystallizing the second organic phase or the third organic phase to obtain the bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide.

Preferably, the method for crystallization includes de-dissolving the second organic phase or the third organic phase under reduced pressure until no solvent is distilled out, and then adding a crystallization solvent for recrystallization to obtain the bis(2) , 4,6-Trimethylbenzoyl) phenylphosphine oxide.

Preferably, the crystallization solvent is selected from hydrocarbons and/or alcohol organic solvents, the hydrocarbons are preferably at least one of petroleum ether, n-hexane, cyclohexane, benzene and toluene; the alcohols are selected from low molecular weight alcohols , preferably methanol and/or ethanol.

Preferably, the temperature of the desolvation under reduced pressure is 75-85°C, for example, 78°C, 80°C or 83°C, and the like.

Preferably, the temperature of the temperature-increasing dissolution process of the recrystallization is 55-65°C, for example, 58°C, 60°C, or 63°C.

Preferably, the temperature of the cooling crystallization process of the recrystallization is less than 10°C, such as 3°C, 5°C or 8°C, and the like.

Preferably, the recrystallization further includes solid-liquid separation and drying.

As a preferred technical solution of the present invention, the preparation method of the bis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide comprises the following steps:

(a) mixing sodium metal with a mass ratio of 1:5 to 15 and a non-polar solvent, heating and heating under a nitrogen atmosphere, and stirring and crushing to obtain a sodium-sand suspension;

(b) making the sodium sand suspension in the step (a) in a reflux state, adding phenylphosphorus dichloride dropwise, and keeping the reflux reaction for 4-10h; then adding the complexing agent dropwise, and continuing to carry out the insulation reflux reaction for 1-6h;

(c) under the protection of nitrogen atmosphere, the reaction solution in step (b) is cooled down, then mes-trimethylbenzoyl chloride is added dropwise, and the reaction is kept at 60～100° C. for 4-10h;

(d) adding water dropwise to the reaction solution obtained in step (c), controlling the temperature to be less than 60° C., stirring and mixing, and then standing to separate liquids to obtain the first organic phase;

(e) adding hydrogen peroxide dropwise to the first organic phase described in step (d), the dropwise addition process is controlled at a temperature of less than 60°C, and after the dropwise addition is completed, the controlled temperature is 30～60°C for 1-3h of insulation reaction; Then stand for liquid separation to obtain the second organic phase;

(f) adding lye to the second organic phase described in step (e), adjusting the pH value to be in the range of 7-11, then stirring at 50-60°C for 0.5-2h, and standing for liquid separation to obtain the third organic phase ;

(g) the third organic phase described in step (f) is carried out under reduced pressure precipitation, until no more solvent is steamed out, then add crystallization solvent, be warming up to complete dissolution, then be cooled to temperature＜10 ℃, solid-liquid separation, Drying gave the bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide.

Compared with the prior art, the present invention has the following beneficial effects:

(1) The preparation method of the present invention adds specific ethers as a complexing agent in the reaction of phenylphosphorus dichloride and sodium sand, which can effectively inhibit the formation of the cluster intermediate of sodium phenylphosphine, and does not require Through the phenylphosphine hydrogen process, the process cost is reduced and the safety of the process is improved;

(2) in the preparation method of the present invention, the complexing agent belongs to the polar aprotic solvent, and the dosage is small, and then the content of organic matter in the waste water can be reduced, and there is a certain environmental benefit;

(3) the preparation method of the present invention improves the reaction rate of the sodium phenylphosphine intermediate and mesityl benzoyl chloride, avoids other side reactions from mesityl benzoyl chloride, and if mesityl benzoyl chloride is in the In the reaction process, the reaction cannot be timely or the reaction is excessive, and by-products such as mes-trimethyl benzoic anhydride and mes-trimethyl benzoate will be produced, and the yield will be reduced, the raw material cost and the purification cost will be reduced simultaneously. Since the preparation method does not produce or less produces the above-mentioned by-products, the residual amount in the kettle is obviously reduced.

Detailed ways

The technical solutions of the present invention are further described below through specific embodiments. It should be understood by those skilled in the art that the embodiments are only for helping the understanding of the present invention, and should not be regarded as a specific limitation of the present invention.

Example 1

The present embodiment provides a preparation method of bis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide, comprising:

(1) In a 500mL four-necked flask, add 11g of sodium metal and 150g of toluene, heat up to 100°C under nitrogen protection, and stir for 3h to beat the sodium metal into sodium sand to obtain a sodium sand suspension;

(2) keep the reflux state, in step (1), add 21g phenyl phosphine dichloride dropwise to the sodium-sand suspension, add about 2h, keep the reflux for 4h, until the reaction solution turns bright yellow, then under the reflux state 4.2g (0.5eq) of tetrahydrofuran was added, the dripping was completed in about 0.5h, the temperature was kept under reflux for 2h, the temperature was lowered to 70°C under nitrogen protection, 43g mes-trimethylbenzoyl chloride was added dropwise, the reaction temperature was controlled at 75°C, the addition was completed in about 2h, and 75°C was added dropwise. Incubate the reaction at ℃ for 8h;

(3) After the reaction in step (2) is completed, add 120 g of water dropwise to the reaction solution, stir at room temperature for 0.5 h, stand for liquid separation to obtain the first organic phase, and dropwise add 30 g of 30% to the first organic phase. After the dropwise addition of hydrogen peroxide, the reaction was kept at 55 °C for 2 h, and the second organic phase was obtained by standing for liquid separation. 100 g of 5wt% sodium carbonate aqueous solution was added to the second organic phase, stirred at 55 °C for 1 h, and allowed to stand for liquid separation. obtaining a third organic phase;

(4) the 3rd organic phase is decompressed under reduced pressure until there is no more toluene to steam out, add the petroleum ether of 70g, be warming up to 60 DEG C of dissolved clear, be slowly cooled to the temperature lower than 10 DEG C and carry out crystallization, filter, dry, obtain double (2,4,6-Trimethylbenzoyl)phenylphosphine oxide.

The yield of the product prepared by the above method was 92.7%, and the HPLC purity was 99.5%.

Example 2

(1) In a 500mL four-neck flask, add 11g of sodium metal and 150g of toluene, add 4.2g (0.5eq) of tetrahydrofuran, heat up to 100°C under nitrogen protection, and stir for 3h to make sodium metal into sodium sand to obtain a sodium sand suspension ;

(2) maintain the reflux state, in step (1), add 21 g of phenyl phosphine dichloride dropwise to the sodium-sand suspension, add it for about 2 hours, and keep refluxing for 4 hours until the reaction solution turns bright yellow, and the nitrogen protection is lowered to 70°C, dropwise add 43g mes-trimethylbenzoyl chloride, control the reaction temperature to 75°C, finish the addition in about 2h, and keep the reaction at 75°C for 8h;

The yield of the product prepared by the above method was 91.0%, and the HPLC purity was 99.2%.

Comparing Example 1 and Example 2, it can be seen that in the preparation method of the present invention, adding tetrahydrofuran as a complexing agent before or after adding phenylphosphine dichloride can effectively improve the yield of sodium phenylphosphine. , thereby improving the efficiency of the subsequent reaction, improving the yield and purity; and adding tetrahydrofuran after adding phenylphosphine dichloride, the effect is better.

Example 3

(1) In a 500mL four-neck flask, add 20g of metallic sodium and 150g of toluene, heat up to 100°C under nitrogen protection, and stir the sodium for 2h to make sodium sand to obtain a sodium sand suspension;

(2) keep the reflux state, add 21 g of phenylphosphine dichloride dropwise to the sodium-sand suspension, add it for about 2 h, keep it at reflux for 6 h, until the reaction solution becomes bright yellow, add 1.7 g of tetrahydrofuran (0.2 g of tetrahydrofuran (0.2 g) under reflux conditions eq), after dropping for about 0.5h, the temperature was kept under reflux for 4h, the temperature was lowered to 70°C under nitrogen protection, 43g of mesityl benzoyl chloride was added dropwise, the reaction temperature was controlled at 70°C, the addition was completed for about 2h, and the reaction was kept at 70°C for 10h;

(3) after the reaction is completed, add 120g of water dropwise to the reaction solution, stir at room temperature for 1h, stand for liquid separation to obtain the first organic phase, dropwise add 40g of 20% hydrogen peroxide to the first organic phase, and complete the dropwise addition After the reaction at 50°C for 2h, stand for liquid separation to obtain the second organic phase, add 200 g of 3% sodium carbonate aqueous solution to the second organic phase, stir at 50°C for 2h, and stand for liquid separation to obtain the third organic phase;

The yield of the product prepared by the above method was 88.6%, and the HPLC purity was 98.8%.

Example 4

(1) In a 500mL four-neck flask, add 10g of metallic sodium and 150g of toluene, heat up to 100°C under nitrogen protection, and stir the sodium for 4h to make sodium sand to obtain a sodium sand suspension;

(2) Add 21g of phenylphosphine dichloride dropwise to the sodium-sand suspension, keep the reflux state, add it for about 2h, keep it under reflux for 5h, until the reaction solution turns bright yellow, add 2.5g (0.3eq) under reflux conditions ) tetrahydrofuran, dripped for about 0.5h, kept at reflux for 3h, lowered the temperature to 80°C under nitrogen protection, added 50g mes-trimethylbenzoyl chloride dropwise, controlled the reaction temperature to 80°C, added it for about 2h, and kept the reaction at 80°C for 6h;

(3) after the reaction is completed, add 120g of water dropwise to the reaction solution, stir at room temperature for 0.5h, stand for liquid separation to obtain the first organic phase, add dropwise 20g of 50% hydrogen peroxide to the first organic phase, and add dropwise After the completion of the reaction at 60°C for 1 hour, stand for liquid separation to obtain the second organic phase, add 60 g of 8% sodium carbonate aqueous solution to the second organic phase, stir at 60°C for 1 hour, and stand for liquid separation to obtain the third organic phase;

The yield of the product prepared by the above method was 90.8%, and the purity was 99.0%.

Example 5

The only difference from Example 1 is that the equimolar amount of tetrahydrofuran in Example 1 is replaced with dioxane, and the rest of the composition and preparation method are the same as those in Example 1.

The yield of the product obtained by using dioxane as the complexing agent was 93.9%, and the purity was 99.2%.

Example 6

The only difference from Example 1 is that the equimolar amount of tetrahydrofuran in Example 1 was replaced with dibenzofuran, and the rest of the composition and preparation method were the same as those in Example 1.

The yield of the product obtained using dibenzofuran as the complexing agent was 90.2%, and the purity was 99.1%.

Example 7

The only difference from Example 1 is that the equimolar amount of tetrahydrofuran in Example 1 was replaced with ethylene glycol dimethyl ether, and the rest of the composition and preparation method were the same as those in Example 1.

The yield of the product obtained by using ethylene glycol dimethyl ether as the complexing agent was 89.7%, and the purity was 99.2%.

Example 8

The only difference from Example 1 is that the equimolar amount of tetrahydrofuran in Example 1 was replaced with anisole, and the rest of the composition and preparation method were the same as those in Example 1.

The yield of the product obtained by using anisole as a complexing agent was 87.5%, and the purity was 98.6%.

From the comparison between Example 1 and Examples 5-8, it can be seen that the method of the present invention uses cyclic ether as the complexing agent, and the activation efficiency is relatively higher; and for the complexing agent in unit molar amount, the higher the content of oxygen element , the activation efficiency is relatively higher.

Example 9

The only difference from Example 1 is that the addition amount of tetrahydrofuran in Example 1 is replaced by 8.4 g (1 eq), and the rest of the composition and preparation method are the same as those in Example 1.

The yield of the product prepared by the above method was 91.4%, and the purity was 98.9%.

Example 10

The only difference from Example 1 is that the second organic phase is directly recrystallized without the alkaline solution treatment step, and the rest of the composition and preparation method are the same as in Example 1.

The yield of the product prepared by the above method was 84.9%, and the purity was 97.5%.

Example 11

The only difference from Example 1 is that the tetrahydrofuran in Example 1 is replaced with 18-crown-6 in an equimolar amount, and the rest of the composition and preparation method are the same as those in Example 1.

The yield of the product prepared by the above method was 89.0%, and the purity was 98.7%.

Example 12

The difference between the present embodiment and Example 1 is that the process of adding metallic sodium in step (1) adds 2g sodium tert-butoxide, and after the mesityl benzoyl chloride is added dropwise, the insulation reaction time is set to 4h (for example 1 half of the reaction time), other parameters and conditions are exactly the same as in Example 1.

The yield of the product prepared by the above method was 90.6%, and the purity was 99.3%.

Example 13

The difference between this example and Example 12 is that the quality of sodium tert-butoxide is replaced with sodium hydroxide, and other parameters and conditions are exactly the same as those in Example 12.

The yield of the product prepared by the above method was 87.8%, and the purity was 99.0%.

Example 14

The difference between this example and Example 12 is that the addition amount of sodium tert-butoxide is replaced by 2.5g, and other parameters and conditions are exactly the same as those in Example 12.

The yield of the product prepared by the above method was 79.5%, and the purity was 98.4%.

The yield drop here is caused by the side reaction caused by the excessive addition of sodium tert-butoxide.

Example 15

The difference between this example and Example 12 is that the addition amount of sodium tert-butoxide is replaced by 0.2 g, and other parameters and conditions are exactly the same as those in Example 12.

The yield of the product prepared by the above method was 78.9%, and the purity was 99.2%.

The decrease in yield here is due to the fact that the amount of tert-butanol added is too small, and the promoting effect on the reaction is insufficient.

Example 16

The difference between this example and Example 12 is that the quality of sodium tert-butoxide is replaced by potassium carbonate, and other parameters and conditions are exactly the same as those in Example 12.

The yield of the product prepared by the above method was 88.0%, and the purity was 99.1%.

Example 17

The difference between this example and Example 12 is that the quality of sodium tert-butoxide is replaced by potassium oxide, and other parameters and conditions are exactly the same as those in Example 12.

The yield of the product prepared by the above method was 84.2%, and the purity was 99.0%.

Comparative Example 1

The only difference from Example 1 is that the addition of tetrahydrofuran is not included in the preparation process, and other preparation methods are the same as those in Example 1.

The yield of the product in this comparative example is 40.8%, and the purity is 90.6%; it can be seen from the comparison between Example 1 and Comparative Example 1 that if no complexing agent is added in the reaction process, the rate of the reaction process will be greatly reduced, thereby affecting the yield of the product.

Comparative Example 2

The only difference from Example 1 is that the tetrahydrofuran in Example 1 is replaced with naphthalene of the same mole number, and the rest of the preparation methods are the same as those in Example 1.

The yield of the product in this comparative example is 50.6%, and the purity is 95.6%;

It can be seen from the comparison between Example 1 and Comparative Example 2 that if tetrahydrofuran is replaced with naphthalene, in the reaction process, more sodium phenylphosphine polyphosphide will be generated, which will affect further reactions. Therefore, when the amount of naphthalene added When the added amount of the complexing agent is the same as that of the present invention, the yield of the obtained product will be significantly reduced.

Comparative Example 3

The only difference from Example 1 is that the tetrahydrofuran in Example 1 is replaced with chlorobenzene of the same mole number, and the rest of the preparation methods are the same as those in Example 1.

The yield of the product in this comparative example is 41.0%, and the purity is 88.2%; it can be seen from the comparison between Example 1 and Comparative Example 3 that if tetrahydrofuran is replaced with chlorobenzene, more phenylphosphine will be generated during the reaction process The sodium polyphosphide affects the further reaction. When the amount of chlorobenzene added is the same as that of the complexing agent in the present invention, the yield of the obtained product will be significantly reduced.

Comparative Example 4

The only difference with Example 1 is that the tetrahydrofuran in Example 1 is replaced with the tert-butyl alcohol of the same mole number, and all the other preparation methods are the same as in Example 1.

In this comparative example, the yield of the product is 52.1%, and the purity is 85%; from the comparison between Example 1 and Comparative Example 4, it can be seen that if tetrahydrofuran is replaced with tert-butanol, the product yield is obviously reduced; and in the reaction process, The addition of tert-butanol will consume sodium metal, and will generate phosphine hydride, which emits a foul odor, and has certain potential safety hazards, which is not conducive to large-scale industrial production and application.

It can be seen from Comparative Example 1 and Comparative Examples 2-4 that, under the condition of the same addition amount, adding the complexing agent of the present invention can achieve the technical effect of effectively inhibiting the formation of sodium phenylphosphine polyphosphide, And then make the product yield improve obviously, and add naphthalene, chlorobenzene and tert-butanol respectively in the comparative example 2-4 to replace the complexing agent in the present invention, compared with the comparative example 1, although its product yield has improved, but The effect is not significant; it is further explained that the above-mentioned ethers with specific structures are added as complexing agents in the method of the present invention, and the improvement effect is the best.

Comparative Example 5

The only difference from Example 1 is that the solvent in Example 1 is replaced with the same volume of tetrahydrofuran, and other preparation methods are the same as those in Example 1.

In this comparative example, the yield of the product is 40.2%, and the purity is 88.4%; meanwhile, the reaction intermediate is insoluble in the solvent, and the reaction is slow. From the comparison of Example 1 and Comparative Example 5, it can be seen that the yield of the obtained product will be greatly reduced by replacing the solvent with tetrahydrofuran.

It can be seen from the comparison between Example 1 and Comparative Example 5 that the complexing agent of the present invention belongs to a polar aprotic solvent, which plays a role in complexing sodium phenylphosphine in the reaction process, thereby inhibiting the increase of sodium phenylphosphine. For the formation of polyphosphide, the reaction process needs to be carried out in a non-polar solvent. Therefore, simply using tetrahydrofuran as the solvent will not only fail to achieve the effect of improving the yield of the product in the present invention, but also significantly reduce the yield of the obtained product.

Comparative Example 6

The only difference from Example 1 is that the solvent toluene in Example 1 is replaced with tetrahydrofuran of the same volume, the complexing agent tetrahydrofuran is replaced with naphthalene of the same molar amount, and the other preparation methods are the same as those of Example 1.

In this comparative example, the yield of the product is 40.5%, and the purity is 90.6%; from the comparison between Example 1 and Comparative Example 6, it can be seen that when the solvent is changed to tetrahydrofuran and the complexing agent is changed to naphthalene, the yield of the obtained product drops significantly .

Comparative Example 7

The only difference from Example 1 is that tetrahydrofuran in Example 1 is replaced with dibenzothiophene, and the rest of the composition and preparation method are the same as those in Example 1.

The yield of the product obtained using dibenzothiophene as a complexing agent was 83.8% and the purity was 95.5%.

Comparative Example 8

The only difference from Example 1 is that tetrahydrofuran in Example 1 is replaced with dimethyl sulfide, and the rest of the composition and preparation method are the same as those in Example 1.

The yield of the product obtained by using dimethyl sulfide as the complexing agent was 80.2%, and the purity was 96.3%.

From the comparison of Example 1 and Comparative Examples 7-8, it can be seen that the heteroatom in the complexing agent of the present invention is selected from oxygen atoms, that is, when the ethers of the above-mentioned specific structure of the present invention are used, the complexation effect is better in the reaction. , and the yield of the obtained product is higher.

In the methods described in the above examples and comparative examples, the materials added by dropwise addition are in liquid or solution state.

Calculation method of product yield: Based on the amount of phenylphosphine dichloride added, the theoretical mass of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide was calculated as m ₁ , and the actual mass was m 1 . The mass of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide obtained after drying was m ₂ , and the yield was calculated from m ₂ /m ₁ ×100%.

The product purity refers to the result of testing by high performance liquid chromatography.

The applicant declares that the above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should Changes or substitutions that can be easily conceived within the technical scope all fall within the protection scope and disclosure scope of the present invention.

Claims

A preparation method of bis(2,4,6-trimethylbenzoyl)phenyl phosphine oxide, characterized in that the method comprises the following steps:

(1) mixing and reacting sodium sand, phenylphosphine dichloride and complexing agent in a non-polar solvent; wherein, the complexing agent is selected from cyclic ethers, ethers shown in formula 1) and those shown in formula 2). at least one of ethers;

Wherein, R 1 , R 2 and R 3 are each independently selected from C1-C4 alkyl; n is selected from 1-20;

(2) in the reaction solution that step (1) obtains, add mes-trimethylbenzoyl chloride to react;

(3) subjecting the product of step (2) to oxidation reaction to obtain the bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide.
The preparation method according to claim 1, wherein the molar ratio of phenylphosphine dichloride to the complexing agent in step (1) is 1:(0.01～2), preferably 1:(0.2～1.0) ;

Preferably, the cyclic ether is selected from tetrahydrofuran, 1,4-dioxane, 15-crown-5, 18-crown-6, 12-crown-4, dicyclohexane-18-crown- 6 and at least one of dibenzofuran, preferably 1,4-dioxane;

Preferably, the complexing agent is selected from
and / or

Preferably, the complexing agent is selected from anisole;

Preferably, in step (1), the mass ratio of sodium sand to phenylphosphine dichloride is 1:(1～2.5), preferably 1:(1.7～2.2);

Preferably, in step (1), the mass ratio of sodium sand to non-polar solvent is 1:5～15;

Preferably, the non-polar solvent includes at least one of toluene, xylene and ethylbenzene.
The preparation method according to claim 1 or 2, characterized in that, the method for mixing reaction in step (1) comprises: in a reflux state, adding phenylphosphine dichloride to the sodium-sand suspension, and performing the first time Reaction, then add complexing agent, carry out the second reaction;

Or, the method for mixing and reacting in step (1) includes: in a reflux state, adding phenylphosphine dichloride to the mixed solution of the sodium sand suspension and the complexing agent to carry out the reaction.
The preparation method of claim 3, wherein the preparation method of the sodium sand suspension comprises: mixing sodium metal and a non-polar solvent, heating under an inert atmosphere, and crushing to obtain the sodium sand suspension;

Preferably, the inert atmosphere includes a nitrogen atmosphere;

Preferably, the method of adding phenylphosphine dichloride is dropwise;

Preferably, the time of the first reaction is 4-10h;

Preferably, the method of adding the complexing agent is dropwise;

Preferably, the time of the second reaction is 1-6h.
The preparation method according to any one of claims 1-4, wherein an alkaline substance is also added in step (1);

Preferably, the basic substance includes at least one of alkali metal hydroxides, oxides, alcohol compounds and carbonates; preferably alkali metal alcohol compounds;

Preferably, the alkali metal hydroxide is selected from sodium hydroxide;

Preferably, the oxide of the alkali metal is selected from potassium oxide;

Preferably, the alkali metal alcoholate is selected from the group consisting of sodium ethoxide, sodium methoxide, sodium butoxide, sodium tert-butoxide, sodium isopropoxide, potassium ethoxide, potassium methoxide, potassium butoxide, potassium tert-butoxide and isopropanol At least one of potassium, preferably sodium tert-butoxide;

Preferably, the alkali metal carbonate is selected from sodium carbonate and/or potassium carbonate;

Preferably, in step (1), the amount of alkaline substance added is 0.1-10% of the mass of phenylphosphine dichloride, preferably 1-5%.
The preparation method according to any one of claims 1-5, wherein the mode of adding mes-trimethylbenzoyl chloride in step (2) is dropwise;

Preferably, the reaction temperature in step (2) is 60-100°C;

Preferably, the time for the reaction described in step (2) is 4-10h;

Preferably, the reaction in step (2) is carried out under the protection of an inert atmosphere.
The preparation method according to any one of claims 1-6, characterized in that, in step (2), after the reaction finishes, it also comprises liquid separation to obtain the first organic phase;

Preferably, the method of the liquid separation is to add water to the solution after the reaction in step (2), and then stand for liquid separation to obtain the first organic phase;

Preferably, the method of adding water is dropwise;

Preferably, the temperature of the liquid separation operation is <60°C.
The preparation method according to claim 7, wherein the method for the oxidation reaction in step (3) comprises adding hydrogen peroxide to the first organic phase to carry out the oxidation reaction;

Preferably, the temperature of the oxidation reaction is 30-60°C;

Preferably, after the oxidation reaction, it also includes standing and liquid separation to obtain the second organic phase;

Preferably, the method further comprises adding lye to the second organic phase to react;

Preferably, the addition amount of the lye is such that the pH value of the solution is 7-11;

Preferably, the solute of the lye is selected from at least one of sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium sulfite and sodium thiosulfate, preferably sodium carbonate;

Preferably, after adding the lye, the temperature for the reaction is 50-60 °C;

Preferably, after adding lye, the reaction time is 0.5～3h;

Preferably, after adding the lye, and after the reaction is completed, it also includes standing for liquid separation to obtain the third organic phase.
The preparation method of claim 8, wherein the method further comprises crystallizing the second organic phase or the third organic phase to obtain the bis(2,4,6-trimethylbenzene) formyl) phenyl phosphine oxide;

Preferably, the method for crystallization includes de-dissolving the second organic phase or the third organic phase under reduced pressure until no solvent is distilled out, and then adding a crystallization solvent for recrystallization to obtain the bis(2) , 4,6-trimethylbenzoyl) phenyl phosphine oxide;

Preferably, the temperature of the decompression precipitation is 75-85°C;

Preferably, the temperature of the temperature-raising dissolution process of the recrystallization is 55-65 °C;

Preferably, the temperature of the cooling crystallization process of the recrystallization is less than 10°C;

Preferably, the recrystallization further includes solid-liquid separation and drying.
The preparation method according to any one of claims 1-9, wherein the method comprises the following steps:

(a) mixing sodium metal with a mass ratio of 1:5 to 15 and a non-polar solvent, heating and heating under a nitrogen atmosphere, and stirring and crushing to obtain a sodium sand suspension;

(b) making the sodium sand suspension in the step (a) in a reflux state, adding phenylphosphorus dichloride dropwise, and keeping the reflux reaction for 4-10h; then adding the complexing agent dropwise, and continuing to carry out the insulation reflux reaction for 1-6h;

(c) under the protection of nitrogen atmosphere, the reaction solution in step (b) is cooled down, then mes-trimethylbenzoyl chloride is added dropwise, and the reaction is kept at 60～100° C. for 4-10h;

(d) adding water dropwise to the reaction solution obtained in step (c), controlling the temperature to be less than 60° C., stirring and mixing, and then standing to separate liquids to obtain the first organic phase;

(e) adding hydrogen peroxide dropwise to the first organic phase described in step (d), the dropwise addition process is controlled at a temperature of less than 60°C, and after the dropwise addition is completed, the controlled temperature is kept for 1-3h at 30～60°C; Then stand for liquid separation to obtain the second organic phase;

(f) adding lye to the second organic phase described in step (e), adjusting the pH value to be in the range of 7-11, then stirring at 50-60°C for 0.5-2h, and standing for liquid separation to obtain the third organic phase ;

(g) the third organic phase described in step (f) is carried out under reduced pressure precipitation, until no more solvent is steamed out, then add crystallization solvent, be warming up to complete dissolution, then be cooled to temperature＜10 ℃, solid-liquid separation, Drying gave the bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide.