Preparation method of 2, 4, 6-tri [(1, 1-biphenyl)-4-yl]-1, 3, 5-triazine

Abstract

The invention discloses a preparation method of 2, 4, 6-tri [(1, 1-biphenyl)-4-yl]-1, 3, 5-triazine, which comprises the following steps: preparing a 4-brominated biphenyl Grignard reagent from 4-brominated biphenyl at 30-60 DEG C through Grignard reaction, dropwise adding the Grignard reagent into a cyanuric chloride solution at-10-10 DEG C, heating to 40-70 DEG C after dropwise adding, reacting, adding water for quenching after the reaction is finished, adjusting the pH value to 5-7, and filtering to obtain the 2, 4, 6-tri [(1, 1-biphenyl)-4-yl]-1, 3, 5-triazine. And recrystallizing the filter cake by using o-dichlorobenzene to obtain the 2, 4, 6-tri [(1, 1-biphenyl)-4-yl]-1, 3, 5-triazine. The method is short in time, high in efficiency and simple in post-treatment, the purity of the obtained product does not need to be specially purified, the purity, the yield and the like are guaranteed, the cost is low, and the method is suitable for large-scale industrial production.

Description

Technical Field

[0001] The invention belongs to the field of organic chemistry, and specifically relates to a method for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine. Background Art

[0002] Excessive exposure to ultraviolet rays can easily cause irreversible denaturation of protein fibers in the dermis of the skin, leading to sagging skin and aggravating skin aging. In severe cases, it can also cause melanin deposition, skin cancer and other diseases. Therefore, in order to ensure human health and safe production and life, it is very necessary to research and develop more effective ultraviolet absorbers.

[0003] 2,4,6-Tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine is a new type of triazine UV absorber with a larger molecular structure, good UV absorption performance, and strong absorption of both UVA and UVB. It is a type of triazine UV absorber currently allowed for use by the US FDA, the European Union, and Japan.

[0004] At present, there are mainly the following methods for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine: The method disclosed in US16349704 is to prepare 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine by Suzuki coupling with phenylboric acid in the presence of Pd(0) catalyst. Due to the use of Pd(0) catalyst, the cost is high and it is not conducive to industrial production.

[0005] The method disclosed in US7311897 includes reacting cyanuric chloride with biphenyl in a molten state in the presence of a catalyst AlCl3, and passing hydrogen chloride to obtain 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine with a yield of 65%. The process uses melting technology, has high energy consumption, and has high requirements for equipment. In addition, the high temperature environment may bring safety hazards. The reaction has many side reactions, the yield is low, and the product purification is difficult, which is not suitable for industrial production.

[0006] US06225467 discloses a preparation method, in which 4-biphenylnitrile is used as a raw material to react in the presence of 4-biphenylcarbonyl chloride, thionyl chloride, aluminum chloride and ammonium chloride to obtain a crude 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine, and then the crude product is purified by sublimation to obtain a finished product; the method uses 4-biphenylcarbonyl chloride at a high cost; the process uses a large amount of inorganic salts to make the content of the prepared crude product low; the patent reports that the product is refined by a sublimation method, which has a long operation time and a large product loss, and is not suitable for the purification of a large amount of products.

[0007] CN106632112 reported that cyanuric chloride can be subjected to multiple Grignard reactions with different Grignard reagents to prepare triazine compounds with different side chains. Patent US2019280211 reported that cyanuric chloride and an equivalent amount of 3-bromobiphenyl were subjected to Grignard reaction to prepare 2,4-dichloro-6-([1,1'-biphenyl]-3-yl)-1,3,5-triazine, and 2,4-dichloro-6-([1,1'-biphenyl]-3-yl)-1,3,5-triazine was then reacted with other side chains to prepare triazine derivatives containing different side chains. These two patents show that triazine derivatives can be prepared by Grignard reaction, but neither of these two patents reported that cyanuric chloride and 4-bromobiphenyl were subjected to a one-step Grignard reaction to prepare 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine.

[0008] The above-mentioned prior art has various deficiencies. Therefore, it is necessary to develop a new method for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine. Summary of the invention

[0009] The object of the present invention is to provide a method for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine, which has high yield, high purity, short reaction time, low energy consumption and is suitable for industrial production.

[0010] In one embodiment, a method for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine of the present invention comprises the following steps:

[0011] 1) 4-bromobiphenyl is added to a tetrahydrofuran solution of magnesium and iodine, and after the reaction is completed, 4-biphenyl magnesium bromide is obtained;

[0012] 2) 4-biphenyl magnesium bromide is reacted with cyanuric chloride to prepare 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine.

[0013] Furthermore, in the preparation method of the present invention, the reaction temperature of step 1) is 30 to 60° C., and the reaction time of step 1) is 1 to 5 hours.

[0014] Preferably, in the above-mentioned preparation method of the present invention, in step 1), the molar ratio of 4-bromobiphenyl, magnesium and iodine is 1: (1.00-1.50): (0.05-0.50).

[0015] Furthermore, in the preparation method of the present invention, the reaction described in step 2) comprises dissolving cyanuric chloride in tetrahydrofuran, lowering the temperature to -10 to 10°C, and dripping the 4-biphenyl magnesium bromide reaction solution obtained in step 1) and, after the dripping is completed, stirring, heating to 40 to 70°C for reaction to obtain 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine.

[0016] Preferably, in the above-mentioned preparation method of the present invention, in step 2), the molar ratio of 4-biphenyl magnesium bromide to cyanuric chloride is (3.60-6.00):1.00.

[0017] The preparation method of the present invention, in step 2), further comprises cooling after the reaction is completed, adding water to quench, adjusting the pH to 5-7 with hydrochloric acid, filtering, recrystallizing the filter cake with an organic solvent, filtering, and drying the filter cake. The reaction time of step 2) is 8-16 hours.

[0018] In the above-mentioned preparation method of the present invention, the organic solvent is o-dichlorobenzene.

[0019] In the above-mentioned preparation method of the present invention, the drying temperature is 30-80°C.

[0020] In a specific embodiment, a method for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine of the present invention comprises the following steps:

[0021] 1) Synthesis of 4-biphenyl magnesium bromide

[0022] Dissolve 4-bromobiphenyl in tetrahydrofuran; drip the 4-bromobiphenyl tetrahydrofuran solution into a mixture solution containing magnesium chips, iodine and tetrahydrofuran, control the temperature at 30-60°C for 1-5 hours after the reaction starts, and lower the temperature of the reaction solution to room temperature for standby use after the reaction ends, wherein the molar ratio of 4-bromobiphenyl, magnesium chips and iodine is 1:(1.00-1.50):(0.05-0.50).

[0023]

[0024] 2) Synthesis of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0025] Dissolve cyanuric chloride in tetrahydrofuran to obtain a cyanuric chloride solution, cool it to -10 to 10°C, control the temperature, directly add the 4-biphenyl magnesium bromide reaction solution (i.e., the reaction product mixed solution) obtained in the previous step dropwise into the cyanuric chloride solution, raise the temperature to 40 to 70°C after the addition is complete, react for 8 to 16 hours, cool it to room temperature after the reaction is complete, add water to quench, adjust the pH to 5 to 7 with acid, and filter; add ethanol or ethyl acetate as a solvent to the filter cake, and wash it by pulping; after washing, dry the filter cake at 30 to 80°C to obtain 2,4,6-tri[(1,1-biphenyl)-4-yl]-1,3,5-triazine.

[0026]

[0027] In a specific embodiment, in step 2), the molar ratio of 4-biphenyl magnesium bromide to cyanuric chloride is 3.60-6.00:1.00.

[0028] In the preparation method of the present invention, the Grignard reagent 4-biphenyl magnesium bromide is appropriately excessive to ensure that cyanuric chloride completely generates a trisubstituted product, and the excess 4-biphenyl magnesium bromide is quenched by adding water and can be effectively removed by subsequent filtration, washing and recrystallization.

[0029] The preparation method of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine of the present invention is short in time, high in efficiency, simple in post-treatment, and relatively low in cost; the obtained product does not need to be specially purified, has good purity and yield, and is suitable for industrial production. DETAILED DESCRIPTION

[0030] The following examples are typical and are used to further illustrate and understand the essence of the present invention, but are not intended to limit the scope of the present invention. Any simple modifications and adaptations made within the essence of the present invention also fall within the scope of the present invention.

[0031] Comparative Example 1

[0032] US2019280211 discloses that a bromo compound reacts with magnesium and iodine at 0°C, and then cyanuric chloride is slowly dripped in to react at 0°C to prepare a substituted triazine compound. According to the disclosure of this patent, 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine is prepared according to this method. 7.86g magnesium and 1.64g iodine are added to 100ml THF, stirred for 30min, 75.3g 4-bromobiphenyl is dissolved in 300ml THF, and the 4-bromobiphenyl solution is dripped into the iodine and magnesium THF solution. The process is controlled at 0°C, stirred for 30min, 15.5g cyanuric chloride is dissolved in 150ml THF, and the prepared Grignard reagent solution is dripped into the cyanuric chloride solution to react at 0°C. After the reaction, water is added to the reaction bottle to quench, filter, and dry the filter cake to obtain 20.7g of the product, with a molar yield of 46% and an HPLC of 76.5%.

[0033] Example 1 Preparation of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0034] 1) Preparation of 4-biphenyl magnesium bromide

[0035] Add 150 ml of tetrahydrofuran, 10.0 g of iodine and 10.0 g of magnesium chips into a 500 ml three-necked flask, stir and heat to 30-60°C to prepare a mixed solution of iodine and magnesium chips in hydrogenfuran;

[0036] 90.0 g of 4-bromobiphenyl is added to 300 ml of tetrahydrofuran to dissolve and prepare a 4-bromobiphenyl solution for use; a portion of the prepared 4-bromobiphenyl solution (accounting for 10-20% of the total amount) is quickly dropped into a mixed solution of iodine and magnesium chips in tetrahydrofuran to initiate a reaction, and the remaining 4-bromobiphenyl solution is slowly dropped into a reaction bottle to react, the process temperature is controlled at 30-60° C., and the reaction is carried out for 2 hours after the addition is completed to obtain a 4-biphenyl magnesium bromide reaction solution.

[0037] 2) Preparation of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0038] In a 1000ml reaction bottle, 18.4g of cyanuric chloride and 60ml of tetrahydrofuran were added, and the temperature was lowered by -10 to 10°C. The 4-biphenyl magnesium bromide reaction solution was added dropwise to the cyanuric chloride solution. After the addition was completed, the mixture was stirred for 10 to 15min, and the temperature was raised to 65 to 70°C for reaction for 10h. After the reaction was completed, the heating was turned off, the temperature was lowered to room temperature, 200ml of water was added to the reaction bottle for quenching, and after the addition of water, the pH was adjusted to 4 to 5 with hydrochloric acid, and the mixture was stirred for 1 to 2h. The filter cake was rinsed with water, and after the filtration was completed, the filter cake was transferred to a reaction bottle, 120ml of o-dichlorobenzene was added for recrystallization, and the filter cake was dried at 30°C for 1h, and then the temperature was raised to 60°C for 7h to obtain 37.9g, with a molar yield of 70.8%, and HPLC: 98.64%.

[0039] Example 2 Preparation of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0040] 1) Synthesis of 4-biphenyl magnesium bromide

[0041] Add 330 ml of tetrahydrofuran, 22.0 g of iodine and 22.2 g of magnesium chips into a 1000 ml three-necked flask, stir and heat to 30-60°C to prepare a mixed solution of iodine and magnesium chips in hydrogenfuran;

[0042] 200.0 g of 4-bromobiphenyl was added into 660 ml of tetrahydrofuran to dissolve, and a 4-bromobiphenyl solution was prepared for use; a portion of the prepared 4-bromobiphenyl solution (accounting for 10-20% of the total amount) was quickly dropped into a mixed solution of iodine and magnesium chips in tetrahydrofuran to initiate a reaction, and then the remaining 4-bromobiphenyl solution was slowly dropped into a reaction bottle. The temperature of the reaction process was controlled at 30-60° C. After the addition was completed, the reaction was carried out for 5 hours to obtain a 4-biphenyl magnesium bromide (reaction product) solution.

[0043] 2) Preparation of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0044] Add 36.8g of cyanuric chloride to a 2000ml reaction bottle, add 120ml of tetrahydrofuran, cool to -10 to 10°C, add 4-biphenyl magnesium bromide solution dropwise to the cyanuric chloride solution, stir for 10 to 15min, heat to 55 to 60°C and react for 15h; after the reaction, turn off the heating and cool to room temperature, add 500ml of water to the reaction bottle to quench, adjust the pH to 4 to 5 with hydrochloric acid after adding water, stir for 1 to 2h, filter, rinse the filter cake with water, transfer the filter cake to the reaction bottle after filtration, add 200ml of o-dichlorobenzene to the filter cake for recrystallization after filtration, filter, dry the filter cake at 30°C for 2h, then heat to 70°C and dry for 7h to obtain 77.6g, with a molar yield of 72.3%, HPLC: 98.43%.

[0045] Example 3 Preparation of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0046] 1) Preparation of 4-biphenyl magnesium bromide

[0047] Add 150 ml of tetrahydrofuran, 10.0 g of iodine and 10.0 g of magnesium chips into a 500 ml three-necked flask, stir and heat to 30-60°C to prepare a mixed solution of iodine and magnesium chips in hydrogenfuran;

[0048] 90.0 g of 4-bromobiphenyl is added to 300 ml of tetrahydrofuran to dissolve and prepare a 4-bromobiphenyl solution for use; a portion of the prepared 4-bromobiphenyl solution (accounting for 10-20% of the total amount) is quickly dropped into a mixed solution of iodine and magnesium chips in tetrahydrofuran to initiate a reaction, and the remaining 4-bromobiphenyl solution is slowly dropped into a reaction bottle to react, the process temperature is controlled at 30-60° C., and the reaction is carried out for 2 hours after the addition is completed to obtain a 4-biphenyl magnesium bromide reaction solution.

[0049] 2) Preparation of 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine

[0050] In a 1000ml reaction bottle, 15g of cyanuric chloride and 60ml of tetrahydrofuran were added, and the temperature was lowered by -10 to 10°C. The 4-biphenyl magnesium bromide reaction solution was added dropwise to the cyanuric chloride solution. After the addition was completed, the mixture was stirred for 10 to 15min, and the mixture was heated to 45 to 50°C for reaction for 12h. After the reaction was completed, the heating was turned off, the mixture was cooled to room temperature, 200ml of water was added to the reaction bottle for quenching, and after the addition of water, the pH was adjusted to 4 to 5 with hydrochloric acid, and the mixture was stirred for 1 to 2h. The mixture was filtered, and the filter cake was rinsed with water. After the filtration was completed, the filter cake was transferred to a reaction bottle, 120ml of o-dichlorobenzene was added for recrystallization, and the filter cake was filtered. The filter cake was dried at 30°C for 1h, and then heated to 60°C for 7h to obtain 30.7g, with a molar yield of 70.2%, and HPLC: 98.28%.

Claims

1. A method for preparing 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine, comprising the following steps: 1) adding 4-bromobiphenyl to a tetrahydrofuran solution of magnesium and iodine to react to obtain 4-biphenyl magnesium bromide; 2) 4-biphenyl magnesium bromide is reacted with cyanuric chloride to prepare 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine.

2. The preparation method according to claim 1, wherein the reaction temperature in step 1) is 30-60°C.

3. The preparation method according to claim 1, wherein the reaction time of step 1) is 1 to 5 hours.

4. The preparation method according to claim 1, wherein in step 1), the molar ratio of 4-bromobiphenyl, magnesium and iodine is 1:(1.00-1.50):(0.05-0.50).

5. The preparation method according to claim 1, wherein the reaction in step 2) comprises dissolving cyanuric chloride in tetrahydrofuran, lowering the temperature to -10 to 10°C, adding 4-biphenyl magnesium bromide in step 1), stirring after the addition, and heating to 40 to 70°C for reaction to obtain 2,4,6-tris[(1,1-biphenyl)-4-yl]-1,3,5-triazine.

6. The preparation method according to claim 1, wherein in step 2), the molar ratio of 4-biphenyl magnesium bromide to cyanuric chloride is (3.60-6.00):1.

00.

7. The preparation method according to claim 1, wherein the reaction time of step 2) is 8 to 16 hours.

8. The preparation method according to claim 5, in step 2), further comprising cooling after the reaction is completed, quenching with water, adjusting the pH to 5-7 with an acid, filtering; recrystallizing the filter cake in an organic solvent, filtering, and drying the filter cake.

9. The preparation method according to claim 8, wherein the acid is hydrochloric acid; or the organic solvent is o-dichlorobenzene.

10. The preparation method according to claim 5, wherein in the reaction of step 2), the 4-biphenyl magnesium bromide of step 1) is added dropwise.

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