Preparation method of a DOPO derivative

Abstract

The present invention discloses a preparation method of a DOPO derivative, which comprises the following steps: S1. Under a nitrogen atmosphere, 1,2-dibromoethane is cooled with liquid nitrogen and injected into a butyllithium solution, and stirred evenly; S2. The raw material (I) is injected therein and reacted at room temperature; S3. The reaction is quenched, the solvent is removed, and an intermediate product is obtained; S4. The intermediate product is dissolved in a solvent, and then a peroxide is added for reaction; S5. The reaction is quenched, the organic phase is extracted, the solvent is removed, and column purification is carried out to obtain the product. In this preparation method, both the intermediate product and the final product are carried out at low temperature or normal temperature, avoiding the adverse effects caused by ultra-high temperature reaction on the reaction substrates and products, and eliminating the unsafe factors in the production process; and the obtained final product has extremely high yield and main component content, and is suitable for large-scale industrial production.

Description

Technical Field

[0001] The present invention relates to the field of flame retardant synthesis, and particularly to a method for preparing DOPO derivatives. Background Art

[0002] DOPO, full name 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide, is an important new type of flame retardant. Flame retardants synthesized from DOPO and its derivatives are environmentally friendly, non-migrating, and have persistent flame retardancy. They can be used in the field of flame retardant treatment of various polymer materials such as various linear polyesters, polyamides, epoxy resins, and polyurethanes. It has been reported that they are widely used in the flame retardancy of materials for electronic devices such as plastics, copper clad laminates, and circuit boards.

[0003] Based on the derivatives obtained after DOPO modification, they well inherit the flame retardant characteristics of DOPO itself and are also the focus of research. The more classic structures and their preparation methods are reported in both Japanese Patent Laid-Open No. 11

[1999] -106619 and Japanese Patent Laid-Open No. P2001-270993A, and another preparation method of this structure is also disclosed in Chinese Patent CN102971333A. This classic structure is essentially a mixture, which contains three isomers, and their structures are shown as follows:

[0004]

[0005] It is reported that in the above mixture, one isomer is the main component, and its content is more than 50% of the mixture. The preparation method adopted is a high-temperature preparation method, and the reaction temperature is maintained at about 200°C for several hours, which is not conducive to the safety and stability of industrial production; and it will cause DOPO to be easily oxidized to acid at high temperature, thereby reducing the purity and yield of the product and bringing difficulties to subsequent separation.

[0006] In summary, how to optimize the preparation method of DOPO derivatives is an urgent problem to be solved. Summary of the Invention

[0007] Based on this, the present invention provides a new method for preparing DOPO derivatives. In this preparation method, both the intermediate product and the final product are carried out at low temperature or normal temperature, avoiding the adverse effects caused by ultra-high temperature reactions on the reaction substrates and products, and eliminating the unsafe factors in the production process; and the yield of the obtained final product is extremely high, which is suitable for large-scale industrial production.

[0008] A method for preparing DOPO derivatives has the following structure:

[0009]

[0010] Among them, the preparation steps of the DOPO derivative include:

[0011] S1. Under a nitrogen atmosphere, cool 1,2-dibromoethane with liquid nitrogen, inject it into a butyllithium solution, and stir evenly.

[0012] S2. Inject raw material (I) into it and react at room temperature.

[0013] S3. Quench the reaction, remove the solvent, and obtain an intermediate product.

[0014] S4. Dissolve the intermediate product in a solvent, and then add a peroxide to react.

[0015] S5. Quench the reaction, extract the organic phase, remove the solvent, purify by column chromatography, and obtain the product.

[0016] Among them, the raw material (I) has the following structure:

[0017]

[0018] Furthermore, in step S1, cool with liquid nitrogen to -60 to -130 °C.

[0019] The specific temperature of cooling with liquid nitrogen in the embodiments of the present invention can be, but is not limited to, -60 °C, -70 °C, -80 °C, -90 °C, -100 °C, -110 °C, -120 °C, -130 °C, or any value between them, such as -78 °C.

[0020] Furthermore, the molar ratio of the raw material (I) to 1,2-dibromoethane is 2:1 - 2.5:1.

[0021] Furthermore, in step S4, the solvent is selected from one or more of dichloromethane, tetrahydrofuran, chloroform, acetone, and dimethylformamide.

[0022] Furthermore, in step S3, the substance used for quenching the reaction is an alcohol.

[0023] The alcohols in the embodiments of the present invention can be, but are not limited to, methanol, ethanol, propanol, butanol, pentanol, hexanol, octanol, etc.

[0024] Furthermore, in step S5, the substance used for quenching the reaction is a sulfite.

[0025] The sulfites in the embodiments of the present invention can be, but are not limited to, sodium sulfite, sodium bisulfite, potassium sulfite, potassium bisulfite, etc.

[0026] Furthermore, in step S1, the stirring time is 0.5 - 2 h.

[0027] Furthermore, in step S4, the reaction is carried out at room temperature.

[0028] Further, in step S5, the mobile phase used for column purification is selected from one or more of dichloromethane, petroleum ether, methanol, ethanol, propanol, cyclohexane, and tetrahydrofuran.

[0029] The peroxides described in the embodiments of the present invention include, but are not limited to, one or more of hydrogen peroxide, sodium peroxide, peracetic acid, potassium peroxide, calcium peroxide, magnesium peroxide, and zinc peroxide.

[0030] Among them, when the peroxide is selected as hydrogen peroxide, it exists in the form of a solution, and the concentration of the solution can be selected from, but not limited to, 10%, 20%, 30%, 40%, 50%, and any value between them, such as 25%. As the experimental concentration, a concentration of about 30% is preferably used.

[0031] When the peroxide is selected as a metal peroxide, it can exist in solid forms such as powder, block, sheet, and floc.

[0032] The present invention has the following beneficial effects:

[0033] 1. The present invention discloses a preparation method of a DOPO derivative, in which the intermediate product and the final product are both carried out at low temperature or normal temperature, avoiding the adverse effects of ultra-high temperature reactions on the reaction substrates and products, and eliminating the unsafe factors in the production process, which is suitable for large-scale industrial production.

[0034] 2. The raw material I used in this preparation method is relatively stable, eliminating the unstable factors in storage and production, which is beneficial to large-scale industrial production.

[0035] 3. This preparation method does not require the additional addition of substances such as catalysts and acid-binding agents. Only butyllithium reagent is needed to activate the reaction. The yield of the obtained final product and the content of the main component in the product are both extremely high, providing a new idea for the preparation of DOPO derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 Shows the phosphorus NMR spectrum of the DOPO derivative obtained in Example 1. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0037] In order to more clearly illustrate the technical solutions of the present invention, the following examples are listed. Unless otherwise specified, the raw materials, reactions, and post-treatment means appearing in the examples are all common raw materials on the market and technical means well-known to those skilled in the art.

[0038] Example 1

[0039] A preparation method of a DOPO derivative is as follows:

[0040]

[0041] (1) Preparation of Intermediate (II):

[0042] Under a nitrogen atmosphere, 1,2-dibromoethane (5 g, 26.9 mmol) was dissolved in dry tetrahydrofuran (200 mL) and cooled to -78 °C. n-Butyllithium (2.4 M, 24.7 mL, 59.2 mmol) was added dropwise using a syringe. Stirring was continued at -78 °C for 40 min. Subsequently, a solution of starting material (I) (15.1 g, 64.56 mmol) in tetrahydrofuran was added via syringe. The mixture was slowly warmed to room temperature and stirring was continued overnight under a nitrogen atmosphere. After the reaction was completed, a small amount of ethanol was added to terminate the reaction. After removing tetrahydrofuran by distillation under reduced pressure, it was first redissolved in dichloromethane, then distilled water was added, and then extraction was carried out with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was removed by distillation under reduced pressure.

[0043] (2) Preparation of Product (III)

[0044] To a solution of intermediate (II) (10 g, 23.5 mmol) in dichloromethane (60 mL) was added hydrogen peroxide (30%, 45 mL). The reaction was stirred overnight at room temperature. After the reaction was completed, an aqueous solution of sodium bisulfite in sufficient amount was added to the reaction mixture to reduce the excess hydrogen peroxide, and extraction was carried out with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was removed by distillation under reduced pressure. Subsequently, separation was carried out by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol, to obtain a white solid product with a yield of 96% (10.3 g).

[0045] It can be seen from Figure 1 that in the DOPO derivative, the content of the main component is extremely high, about more than 90% of the product, while the small peaks on the right are the contents of isomers with a structure similar to the main component, accounting for about 10%.

[0046] Example 2

[0047] A preparation method of a DOPO derivative is as follows:

[0048]

[0049] (1) Preparation of Intermediate (II):

[0050] Under a nitrogen atmosphere, 1,2-dibromoethane (8 g, 43.04 mol) was dissolved in dry tetrahydrofuran (200 mL), and the solution was cooled to -80 °C. n-Butyllithium (2.4 M, 39.5 mL, 94.7 mmol) was added dropwise using a syringe. Stirring was continued at -80 °C for 60 min. Subsequently, a solution of starting material (I) (24.2 g, 103.3 mmol) in tetrahydrofuran was added via syringe. The mixture was slowly warmed to room temperature and stirring was continued overnight under a nitrogen atmosphere. After completion of the reaction, a small amount of ethanol was added to terminate the reaction. After removing tetrahydrofuran by distillation under reduced pressure, the residue was redissolved in dichloromethane, distilled water was added, and then extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure.

[0051] (2) Preparation of product (III)

[0052] To a solution of intermediate (II) (12 g, 28.2 mmol) in tetrahydrofuran (75 mL) was added hydrogen peroxide (30%, 48 mL). The reaction was stirred overnight at room temperature. After completion of the reaction, an aqueous solution of sodium bisulfite in an amount sufficient to reduce the excess hydrogen peroxide was added to the reaction mixture, and extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. Subsequently, separation was carried out by column chromatography using a mixed solvent of dichloromethane and ethanol as the eluent to obtain a white solid product in a yield of 95% (12.3 g).

[0053] Example 3

[0054] A method for preparing a DOPO derivative is as follows:

[0055]

[0056] (1) Preparation of intermediate (II):

[0057] Under a nitrogen atmosphere, 1,2-dibromoethane (8 g, 43.04 mol) was dissolved in dry tetrahydrofuran (200 mL), and the solution was cooled to -78 °C. n-Butyllithium (2.4 M, 39.5 mL, 94.7 mmol) was added dropwise using a syringe. Stirring was continued at -78 °C for 80 min. Subsequently, a solution of starting material (I) (24.2 g, 103.3 mmol) in tetrahydrofuran was added via syringe. The mixture was slowly warmed to room temperature and stirring was continued overnight under a nitrogen atmosphere. After completion of the reaction, a small amount of ethanol was added to terminate the reaction. After removing tetrahydrofuran by distillation under reduced pressure, the residue was redissolved in dichloromethane, distilled water was added, and then extraction was performed with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure.

[0058] (2) Preparation of product (III)

[0059] To a solution of intermediate (II) (13 g, 30.5 mmol) in tetrahydrofuran (80 mL) was added hydrogen peroxide (30%, 45 mL). The reaction was stirred overnight at room temperature. After the reaction was completed, an aqueous solution of sodium bisulfite in sufficient amount was added to the reaction mixture to reduce the excess hydrogen peroxide, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. Subsequently, separation was carried out by column chromatography using a mixed solvent of dichloromethane and ethanol as the eluent to obtain a white solid product with a yield of 95% (13.3 g).

[0060] Example 4

[0061] A method for preparing a DOPO derivative is as follows:

[0062]

[0063] (1) Preparation of intermediate (II):

[0064] Under a nitrogen atmosphere, 1,2-dibromoethane (8 g, 43.04 mol) was dissolved in dry tetrahydrofuran (200 mL) and cooled to -85 °C. n-Butyllithium (2.4 M, 39.5 mL, 94.7 mmol) was added dropwise using a syringe. Stirring was continued at -85 °C for 70 min. Subsequently, a solution of starting material (I) (24.2 g, 103.3 mmol) in tetrahydrofuran was added through a syringe. The mixture was slowly warmed to room temperature and stirred overnight under a nitrogen atmosphere. After the reaction was completed, a small amount of ethanol was added to terminate the reaction. After removing tetrahydrofuran by distillation under reduced pressure, it was redissolved in dichloromethane, then distilled water was added, and then extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure.

[0065] (2) Preparation of product (III)

[0066] To a solution of intermediate (II) (13 g, 30.5 mmol) in tetrahydrofuran (80 mL) was added hydrogen peroxide (30%, 48 mL). The reaction was stirred overnight at room temperature. After the reaction was completed, an aqueous solution of sodium bisulfite in sufficient amount was added to the reaction mixture to reduce the excess hydrogen peroxide, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by distillation under reduced pressure. Subsequently, separation was carried out by column chromatography using a mixed solvent of dichloromethane and ethanol as the eluent to obtain a white solid product with a yield of 96% (13.4 g).

[0067] Example 5

[0068] A method for preparing a DOPO derivative is as follows:

[0069]

[0070] (1) Preparation of Intermediate (II):

[0071] Under a nitrogen atmosphere, 1,2-dibromoethane (8 g, 43.04 mol) was dissolved in dry tetrahydrofuran (200 mL) and cooled to -78 °C. n-Butyllithium (2.4 M, 39.5 mL, 94.7 mmol) was added dropwise using a syringe. Stirring was continued at -78 °C for 100 min. Subsequently, a solution of starting material (I) (24.2 g, 103.3 mmol) in tetrahydrofuran was added via syringe. The mixture was slowly allowed to warm to room temperature and stirring was continued overnight under a nitrogen atmosphere. After the reaction was completed, a small amount of ethanol was added to terminate the reaction. After removing tetrahydrofuran by distillation under reduced pressure, it was first redissolved in dichloromethane, then distilled water was added, and then extraction was carried out with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was removed by distillation under reduced pressure.

[0072] (2) Preparation of Product (III)

[0073] Hydrogen peroxide (25%, 55 mL) was added to a solution of intermediate (II) (13 g, 30.55 mmol) in tetrahydrofuran (80 mL). The reaction was stirred overnight at room temperature. After the reaction was completed, an aqueous solution of sodium bisulfite in sufficient amount was added to the reaction mixture to reduce the excess hydrogen peroxide, and extraction was carried out with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was removed by distillation under reduced pressure. Subsequently, separation was carried out by column chromatography, and the eluent was a mixed solvent of dichloromethane and ethanol, to obtain a white solid product with a yield of 95% (13.3 g).

[0074] The product described in the examples of the present invention is a product mixed with three isomers. In the mixture, the proportion of the isomer as the main component was calculated by integrating the phosphorus nuclear magnetic spectrum, and the results are shown in the following table.

[0075] Table 1 Proportion of the isomer as the main component in the product

[0076] Example Percentage of main component (%) Example 1 0.91 Example 2 0.90 Example 3 0.90 Example 4 0.89 Example 5 0.90

[0077] As can be seen from the above examples, when preparing DOPO derivatives using the technical solution of the present invention, the yield of the finally separated product can be maintained above 95%, showing a significant improvement compared to the yields (80 - 85%) reported in the prior art; and the proportion of the main component in the product is also in an absolutely dominant position.

[0078] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above-described exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be embraced within the present invention.

[0079] In addition, it should be understood that although this specification is described in terms of embodiments, not every embodiment only contains an independent technical solution. This narrative manner of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A preparation method of a DOPO derivative, characterized in that, The DOPO derivative has the following structure: Among them, the preparation steps of the DOPO derivative include: S1. Under a nitrogen atmosphere, cool 1,2-dibromoethane with liquid nitrogen, inject it into a butyllithium solution, and stir evenly; S2. Inject raw material I into it and react at room temperature; S3. Quench the reaction, remove the solvent, and obtain an intermediate product; S4. Dissolve the intermediate product in a solvent, and then add a peroxide to react; S5. Quench the reaction, extract the organic phase, remove the solvent, purify by column chromatography, and obtain the product; Among them, raw material I has the following structure: In step S1, cool with liquid nitrogen to -60 to -130 °C.

2. The preparation method of the DOPO derivative according to claim 1, characterized in that, The molar ratio of raw material I to 1,2-dibromoethane is 2:1 - 2.5:

1.

3. The preparation method of the DOPO derivative according to claim 1, characterized in that, In step S4, the solvent is selected from one or more of dichloromethane, tetrahydrofuran, chloroform, acetone, and dimethylformamide.

4. The preparation method of the DOPO derivative according to claim 1, characterized in that, In step S3, the substance used for quenching the reaction is an alcohol.

5. The preparation method of the DOPO derivative according to claim 1, characterized in that, In step S5, the substance used for quenching the reaction is a sulfite.

6. The preparation method of the DOPO derivative according to claim 1, wherein In step S1, the stirring time is 0.5 - 2 h.

7. The preparation method of the DOPO derivative according to claim 1, characterized in that, In step S4, the reaction is carried out at room temperature.

8. The preparation method of the DOPO derivative according to claim 1, characterized in that, In step S5, the mobile phase used for purification by column chromatography is selected from one or several of dichloromethane, petroleum ether, methanol, ethanol, propanol, cyclohexane, and tetrahydrofuran.

Images