A method for microwave synthesis of 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphepin-6-oxide

Abstract

The application provides a method for synthesizing 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphepin-6-oxide by microwave, and belongs to the technical field of organic synthesis. The method uses diethyl phosphite as a reaction raw material and a solvent, and reacts with antioxidant 2246 in a microwave reactor, and the target product is obtained after purification. The microwave heating technology is adopted, and by accurately controlling the temperature, power and time and other key parameters, the reaction is quickly completed under mild conditions, the reaction time is greatly shortened, the energy consumption is reduced, and the post-treatment operation is simplified. The purity of the obtained product reaches more than 99%, and the yield reaches more than 90%. Meanwhile, the remaining diethyl phosphite filtrate after the reaction is completed can be recycled after distillation recovery, and the discharge of organic waste liquid is reduced. Compared with the prior art, the application has the advantages of mild conditions, high efficiency, high yield, green environmental protection and the like, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for microwave synthesis of 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-6-oxide. Background Technology

[0002] 4,8-Di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-octylphosphine-6-oxide (hereinafter referred to as Compound 1, chemical structure as follows) is an important cyclic phosphite intermediate with high reactivity. It can react with a variety of acyl chloride compounds and is used to prepare a series of ultraviolet absorbers. It has broad application prospects in the field of photostabilization of polymer materials.

[0003] Currently, there are reported methods for synthesizing compound 1. Takaaki Yano et al. (Synthetic Approach to Benzocyclobutenones Using Visible Light and a Phosphonate Auxiliary, Organic Letters, 2018, vol. 20, #4) disclosed a method to prepare compound 1 by reacting diethyl phosphite and antioxidant 2246 as raw materials at 150°C and 35 Torr under reduced pressure for 90 hours. However, this method has problems such as high requirements for reaction equipment, high reaction temperature, long reaction time, high energy consumption, and low yield, which are not conducive to industrial production.

[0004] B. Hari Babu et al. (Synthesis and Bioactivity of Novel Bisphosphonate Derivatives, Heterocycles, Vol. 75, No. 3, 2008) reported another synthetic route, in which antioxidant 2246 is first reacted with phosphorus trichloride to generate a chlorinated intermediate, which is then reacted in ethanol in the presence of triethylamine to obtain compound 1. This process has an overall yield of only about 60% in both steps, and uses large amounts of phosphorus trichloride and triethylamine, generating a large amount of acidic and alkaline waste liquid, which is environmentally unfriendly and does not meet the requirements of green chemistry development.

[0005] In summary, existing methods for preparing compound 1 generally suffer from drawbacks such as harsh reaction conditions (high temperature, long time, negative pressure), cumbersome operation, low yield, and serious environmental pollution. There is an urgent need to develop a new synthetic process that is mild, efficient, environmentally friendly, and suitable for large-scale production. Summary of the Invention

[0006] To address the problems existing in the prior art, the present invention provides a method for microwave synthesis of 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-octylphosphine-6-oxide, the method comprising the following steps: adding diethyl phosphite and antioxidant 2246 to the reaction vessel of a microwave reactor for reaction, purifying, to obtain compound 1, namely 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-octylphosphine-6-oxide; The reaction temperature is 85-105℃, the microwave power is 400-900w, and the reaction time is 10-35 minutes; the mass ratio of diethyl phosphite to antioxidant 2246 is (1.1-4.0):1.

[0007] Furthermore, the reaction temperature is 90-100℃, the microwave power is 500-700w, and the reaction time is 15-30 minutes.

[0008] Furthermore, the reaction temperature is 90°C, 95°C, or 100°C, the microwave power is 500W, 550W, 600W, 650W, or 700W, and the reaction time is 15, 20, 25, or 30 minutes.

[0009] Furthermore, the reaction temperature is 100°C, the microwave power is 700W, and the reaction time is 30 minutes.

[0010] Furthermore, the mass ratio of diethyl phosphite to antioxidant 2246 is (1.5-3.0):1.

[0011] Furthermore, the mass ratio of diethyl phosphite to antioxidant 2246 is 1.5:1, 2.0:1, 2.5:1, or 3.0:1.

[0012] Furthermore, the mass ratio of diethyl phosphite to antioxidant 2246 is 3.0:1.

[0013] Furthermore, the purification method is as follows: filter the system after the reaction is completed, and dry the filter cake.

[0014] Furthermore, the method also includes the following operations: collecting the filtered filtrate and recovering diethyl phosphite by vacuum distillation.

[0015] Furthermore, the HPLC purity of the obtained 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-octylphosphine-6-oxide was ≥99%, and the reaction yield was ≥90%.

[0016] Compared with the prior art, the microwave synthesis method of 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-6-oxophosphate of the present invention has the following significant advantages: (1) The present invention uses microwave heating technology to enable the reaction to be completed quickly under mild conditions, which greatly shortens the reaction time, significantly reduces energy consumption, simplifies post-processing operations, effectively reduces production costs, and is more suitable for industrial production.

[0017] (2) By precisely controlling the key process parameters of the microwave reaction (especially temperature, power and time), the present invention can obtain the target product with high selectivity, the product purity can reach more than 99%, and the reaction yield can reach more than 90%, which is a significant improvement over the prior art.

[0018] (3) In the method of the present invention, diethyl phosphite is used as both a reactant and a solvent. After the reaction is completed, the remaining diethyl phosphite filtrate can be recycled after simple distillation, which reduces the discharge of organic waste liquid and meets the requirements of green environmental protection and atom economy.

[0019] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0020] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0021] Figure 1 This is the HPLC spectrum of the product obtained in Example 1 of the present invention.

[0022] Figure 2 This is the mass spectrum of the product obtained in Example 1 of the present invention. Detailed Implementation

[0023] The raw materials and equipment used in this invention are all known products, obtained by purchasing commercially available products.

[0024] The synthetic route of this invention is as follows: Example 1: Method for microwave synthesis of compound 1 42.5 g (0.125 mol) of antioxidant 2246 and 63.8 g (1.5 W) of diethyl phosphite were added to a reaction flask. The flask was placed in a microwave reactor with a condenser installed. The microwave reactor temperature was adjusted to 90 °C, power to 500 W, and reaction time to 15 minutes. Samples were taken for monitoring to determine when the reaction reached its endpoint. The reaction solution was cooled to 20-30 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 52.5 g of solid, with a yield of 92.0% and a purity of 99.77%. Figure 1 The image shows the HPLC spectrum of the obtained product. Figure 2 This is the mass spectrum of the product obtained in Example 1 of the present invention.

[0025] Example 2: Method for microwave synthesis of compound 1 68 g (0.2 mol) of antioxidant 2246 and 136 g (2.0 W) of diethyl phosphite were added to the reaction flask. The flask was then placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 100 °C, the power to 600 W, and the reaction time to 20 minutes. Samples were taken for monitoring to ensure the reaction reached its endpoint. The reaction solution was cooled to 20-30 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 69.6 g of solid, with a yield of 90.0% and a purity of 99.2%.

[0026] Example 3: Method for microwave synthesis of compound 1 68 g (0.2 mol) of antioxidant 2246 and 204 g (3.0 W) of diethyl phosphite were added to the reaction flask. The flask was then placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 100 °C, the power to 700 W, and the reaction time to 30 minutes. Samples were taken for monitoring to determine when the reaction reached its endpoint. The reaction solution was cooled to 10-20 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 73.3 g of solid, with a yield of 95.0% and a purity of 99.0%.

[0027] Example 4: Method for microwave synthesis of compound 1 68g (0.2mol) of antioxidant 2246 and 170g (2.5w) of diethyl phosphite were added to the reaction flask. The reaction flask was placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 100℃, the power to 700w, and the reaction time to 25 minutes. Samples were taken for monitoring to detect when the reaction reached the endpoint. The reaction solution was cooled to 10~20℃ and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40~50℃ to obtain 70.2g of solid, with a yield of 91.0% and a purity of 99.2%.

[0028] The following is a control method for synthesizing compound 1.

[0029] Comparative Example 1: Method for Microwave Synthesis of Compound 1 68 g (0.2 mol) of antioxidant 2246 and 272 g (4.0 W) of diethyl phosphite were added to the reaction flask. The flask was then placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 80 °C, the power to 500 W, and the reaction time to 15 minutes. During sampling, approximately 30% of the raw materials remained. The reaction solution was cooled to 10-20 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 46.4 g of a light yellow solid, with a yield of 60.0% and a purity of 95.2%.

[0030] Comparative Example 2: Method for Microwave Synthesis of Compound 1 68 g (0.2 mol) of antioxidant 2246 and 272 g (4.0 W) of diethyl phosphite were added to the reaction flask. The flask was then placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 140 °C, the power to 600 W, and the reaction time to 15 minutes. A sample was taken for control, and approximately 20% of the raw material residue was detected. The reaction solution was cooled to 10-20 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 54.8 g of a light yellow solid, with a yield of 71.0% and a purity of 96.1%.

[0031] Comparative Example 3: Method for Microwave Synthesis of Compound 1 68 g (0.2 mol) of antioxidant 2246 and 340 g (5.0 W) of diethyl phosphite were added to the reaction flask. The flask was then placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 110 °C, the power to 600 W, and the reaction time to 40 minutes. During sampling, approximately 15% of the raw material remained. The reaction solution was cooled to 10-20 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 50.2 g of a light yellow solid, with a yield of 65.0% and a purity of 98.0%.

[0032] Comparative Example 4: Method for Microwave Synthesis of Compound 1 68 g (0.2 mol) of antioxidant 2246 and 54.4 g (0.8 W) of diethyl phosphite were added to the reaction flask. The flask was then placed in the condenser tube of a microwave reactor. The microwave reactor temperature was adjusted to 120 °C, power to 500 W, and reaction time to 5 minutes. During sampling, approximately 50% of the raw materials remained. The reaction solution was cooled to 10-20 °C and filtered. The filtrate was distilled under reduced pressure to obtain diethyl phosphite for recycling. The filter cake was dried under reduced pressure at 40-50 °C to obtain 30.9 g of a light yellow solid, with a yield of 40.0% and a purity of 92.0%.

[0033] Comparative Example 5: Compound 1 was synthesized according to the method described in the literature (Takaaki Yano et al., Synthetic Approach to Benzocyclobutenones Using Visible Light and a Phosphonate Auxiliary, Organic Letters, 2018, vol. 20, #4). 68 g (0.2 mol) of antioxidant 2246 and 80.2 g (1.18 w) of diethyl phosphite were added to a reaction flask, and the mixture was stirred at 150 °C and 35 Torr for 90 hours. During the control sampling, approximately 5% of the raw material was detected as residue. The reaction solution was cooled to 10–20 °C and filtered. The filter cake was dried under reduced pressure at 40–50 °C to obtain 69.5 g of a light yellow solid, with a yield of 75.0% and a purity of 98.0%.

[0034] Table 1. Comparison of reaction conditions and product yield and purity for each example and control example. As can be seen, compared with the synthesis method in the literature (Takaaki Yano et al. (Synthetic Approach to Benzocyclobutenones Using Visible Light and a Phosphonate Auxiliary, Organic Letters, 2018, vol. 20, #4)), the microwave synthesis method of compound 1 in Examples 1-4 of this invention has simpler equipment requirements, milder reaction conditions, shorter reaction time, and significantly improved product yield and purity. Compared with the microwave synthesis method of compound 1 in Comparative Examples 1-4, the microwave synthesis method of compound 1 in Examples 1-4 of this invention simultaneously controls the temperature, power, and time during the reaction process, significantly improving product yield and purity.

Claims

1. A method for microwave synthesis of 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-6-oxide, characterized in that, The method includes the following steps: adding diethyl phosphite and antioxidant 2246 into the reaction vessel of a microwave reactor, reacting, purifying, to obtain compound 1, namely 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-6-oxide; The reaction temperature is 85-105℃, the microwave power is 400-900w, and the reaction time is 10-35 minutes; the mass ratio of diethyl phosphite to antioxidant 2246 is (1.1-4.0):

1.

2. The method according to claim 1, characterized in that, The reaction temperature is 90-100℃, the microwave power is 500-700w, and the reaction time is 15-30 minutes.

3. The method according to claim 2, characterized in that, The reaction temperature is 90℃, 95℃ or 100℃, the microwave power is 500w, 550w, 600w, 650w or 700w, and the reaction time is 15, 20, 25 or 30 minutes.

4. The method according to claim 3, characterized in that, The reaction was carried out at a temperature of 100°C, with a microwave power of 700W, and for a reaction time of 30 minutes.

5. The method according to claim 1, characterized in that, The mass ratio of diethyl phosphite to antioxidant 2246 is (1.5-3.0):

1.

6. The method according to claim 5, characterized in that, The mass ratio of diethyl phosphite to antioxidant 2246 is 1.5:1, 2.0:1, 2.5:1, or 3.0:

1.

7. The method according to claim 6, characterized in that, The mass ratio of diethyl phosphite to antioxidant 2246 is 3.0:

1.

8. The method according to any one of claims 1-7, characterized in that, The purification method is as follows: after the reaction is completed, the system is filtered, and the filter cake is dried.

9. The method according to claim 8, characterized in that, The method further includes the following steps: collecting the filtered filtrate and recovering diethyl phosphite by vacuum distillation.

10. The method according to any one of claims 1-7, characterized in that, The HPLC purity of the obtained 4,8-di-tert-butyl-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxane-octylphosphine-6-oxide was ≥99%, and the reaction yield was ≥90%.

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