A method for synthesizing key intermediates of UV-627 based on photocatalytic strategy

Abstract

The invention provides a method for synthesizing a key intermediate of an ultraviolet absorber UV-627 based on a photocatalytic strategy. The invention uses a specific photocatalyst to directly photocatalyze cyanuric chloride and anisole for arylation reaction in air and at room temperature to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution, then add resorcinol and a base to react, filter, concentrate the filtrate under reduced pressure, add a saturated aqueous solution of ammonium chloride, precipitate a solid, filter and wash the filter cake with water, and then dry to obtain 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-[1,3,5]triazine. The method of the invention is simple to operate, green and environmentally friendly, has low raw material cost and low production safety risk.

Description

Technical Field

[0001] The invention belongs to the field of chemical synthesis, and specifically relates to a method for synthesizing 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine, a key intermediate of an ultraviolet absorber UV-627, based on a photocatalytic strategy. Background Art

[0002] The chemical name of UV absorber UV-627 is 2,4-di[2-hydroxy-4-(2-ethylhexyloxy)phenyl]-6-(4-methoxyphenyl)-1,3,5-triazine, which belongs to the triazine UV absorber series. It has the advantages of stable structure, good solubility, light stability, small dosage but strong protection ability. It can effectively protect UV-A and UV-B in a broad spectrum and is widely used in skin care products, coatings, high-end materials and other industries. 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine is the key intermediate for the preparation of UV-627.

[0003] At present, the main synthesis method for preparing 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine (based on the invention patent application records with publication numbers US5955060 and EP3297993) is to first use 4-bromoanisole and magnesium to react to prepare 4-methoxyphenyl magnesium bromide Grignard reagent, then react it with cyanuric chloride to obtain 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine by nucleophilic substitution reaction, and then react with resorcinol under the action of aluminum chloride to undergo Friedel-Crafts arylation reaction, and finally hydrolyze and recrystallize with hydrochloric acid solution to obtain the intermediate. The total yield of the two-step reaction is 63-84%. The reaction equation is as follows:

[0004]

[0005] The first step in the preparation method of the invention patent applications with publication numbers US5955060 and EP3297993 requires the use of relatively expensive 4-bromoanisole as a starting raw material, and a large amount of heat is suddenly released during the preparation of the Grignard reagent, causing the reaction system to overheat and easily cause material rushing, posing a large safety risk; the second step reaction requires the use of anhydrous aluminum chloride, and post-treatment requires the use of a hydrochloric acid solution, so a large amount of high-salt, high-COD wastewater that is difficult to treat is generated during the production process.

[0006] The method disclosed in the invention patent application with publication number CN109879822 is to use anisole with a lower price as the starting material, and solid-supported aluminum chloride catalyzes the reaction with cyanuric chloride to obtain an intermediate 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution, and then add resorcinol, cyclopentane, and solid-supported aluminum chloride to react continuously, and finally add water to quench the reaction, and filter to obtain 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine. The total yield of the two-step reaction is 64~86%. The reaction equation is as follows:

[0007]

[0008] Compared with the existing Grignard reaction preparation process, although the method of the invention patent application with publication number CN109879822 has lower cost and higher safety, the reaction temperature is relatively high (60-90°C) and a large amount of acidic wastewater is generated.

[0009] Compared with traditional synthesis methods, photocatalytic strategies are simpler and safer to operate, and the reaction conditions are milder and greener (Chem. Rev., 2013, 113, 5322; Chem. Rev., 2016, 116, 10075.). The reason why light can promote the reaction is that photocatalysts can transfer light energy to some light-insensitive reactants to improve or expand their photosensitivity, thereby promoting the occurrence of the reaction. For example, under the action of light and photocatalysts, chlorinated (hetero) aromatics break C–Cl bonds to form carbon radicals, which then react with aromatics, alkenes, alkynes, etc. to construct new C–C bonds (J. Am. Chem. Soc. 2018, 140, 9751-9757.). Summary of the invention

[0010] In view of the problems existing in the prior art, the present invention intends to provide a method for synthesizing a key intermediate of an ultraviolet absorber UV-627 based on a photocatalytic strategy, which has mild reaction conditions, simple operation, low cost, and low production safety risk. The technical solution adopted by the present invention to solve the problems existing in the prior art is as follows:

[0011] A method for synthesizing a key intermediate of an ultraviolet absorber UV-627 based on a photocatalytic strategy comprises the following steps:

[0012] Step 1: Add anisole, cyanuric chloride, solvent, base and photocatalyst into a reaction container, and react for 6-24 hours at room temperature under CFL irradiation to obtain 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution;

[0013] Step 2: adding resorcinol and a base to the 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution obtained in step 1, and then reacting at room temperature under CFL irradiation for 6-24 hours;

[0014] Step 3: Filter the reaction solution of step 2, concentrate the filtrate under reduced pressure, add saturated aqueous ammonium chloride solution, precipitate solid, filter, wash the filter cake with water, and dry at 40-100° C. to obtain 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine.

[0015] The chemical structure of the obtained 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine is as follows:

[0016]

[0017] The reaction equation of the method of the present invention is as follows:

[0018]

[0019] The photocatalyst in step 1 and step 2 is one of quinones, quinolines and xanthan dyes. Preferably, the photocatalyst includes eosin Y, anthraquinone and triarylpyran. The photocatalyst has a great influence on the conversion rate of the reaction.

[0020] The lighting conditions in step 1 and step 2 are room temperature, and the irradiation intensity of the CFL lamp is 23-46W, preferably 32-36W.

[0021] In the step 1, the molar ratio of cyanuric chloride to anisole is 1:1.0-1:1.5, and the preferred molar ratio is 1:1.1-1:1.2; the molar ratio of the photocatalyst to cyanuric chloride is 1:50-1:10, and the preferred molar ratio is 1:20-1:17; the solvent is dimethyl sulfoxide, acetonitrile, tetrahydrofuran or 1,2-dichloroethane; the mass ratio of the solvent to cyanuric chloride is 6:1-10:1, and the preferred mass ratio is 7:1-9:1. Too much solvent will slow down the reaction speed, and too little solvent will make stirring difficult; the base is an inorganic base, preferably sodium hydroxide, potassium hydroxide, potassium tert-butoxide or sodium tert-butoxide, and the choice of the base directly affects the reaction efficiency; the molar ratio of the base to cyanuric chloride is 1:1.1-1:1.5, and the preferred molar ratio is 1:1.2-1:1.3. The specific reaction time is determined according to the conversion rate detected by the central control. After 4 hours of reaction, sampling and monitoring are carried out every hour. When the conversion rate does not increase, the reaction is stopped. The reaction time is 6-24 hours, and the preferred reaction time is 8-10 hours.

[0022] The molar ratio of resorcinol in step 2 to cyanuric chloride added in step 1 is 2.1:1-2.4:1, and the preferred molar ratio is 2.1:1-2.2:1; the base is an organic base or an inorganic base, preferably dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate or triethylamine, and the choice of the base directly affects the reaction efficiency; the molar ratio of the base to resorcinol is 2.1:1-3.0:1, and the preferred molar ratio is 2.2:1-2.4:1. The specific reaction time is determined according to the conversion rate detected by the central control. After 4 hours of reaction, sampling and monitoring are performed every 1 hour. When the conversion rate does not increase, the reaction is stopped. The reaction time is 6-24 hours, and the preferred reaction time is 12-18 hours.

[0023] In step 3, the filtrate is concentrated under reduced pressure to 5-20% of the original volume, preferably, concentrated under reduced pressure to 5-10% of the original volume; the mass ratio of saturated ammonium chloride aqueous solution to cyanuric chloride added in step 1 is 10:1-30:1, preferably 18:1-23:1; the product is dried at 40-60°C, preferably at 50-60°C.

[0024] The present invention has the following advantages:

[0025] (1) Compared with the existing preparation processes of Grignard reaction and Friedel-Crafts reaction, the present invention adopts a photocatalytic method, which has mild reaction conditions, is green and environmentally friendly, and greatly reduces production safety risks;

[0026] (2) The one-pot continuous reaction technology is adopted, and a photocatalyst is used to carry out a two-step reaction, which reduces the separation process, makes the operation simpler, and reduces production costs and equipment investment.

[0027] (3) Compared with the reported preparation processes, all operations of the present invention do not require nitrogen protection and are carried out in air, which reduces the operation process and reduces the cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine prepared in Example 1 is 1 H NMR spectrum;

[0029] Figure 2 The 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine prepared in Example 1 is 13 C NMR spectrum;

[0030] Figure 3 The infrared spectrum of 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine synthesized by the method of Example 1 of the present invention;

[0031] Figure 4 This is a liquid chromatogram of 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine synthesized in Example 1 of the present invention. DETAILED DESCRIPTION

[0032] The technical solution of the present invention is further specifically described below through embodiments and in conjunction with the accompanying drawings.

[0033] Example 1

[0034] In air, 18.4 g of cyanuric chloride, 11.9 g of anisole, 3.5 g of eosin Y, 5.2 g of sodium hydroxide and 147 g of dimethyl sulfoxide were added to a 500 mL reaction bottle, irradiated with a 36 W CFL, and stirred at room temperature for 8 h to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution. The conversion rate was 95% as detected by HPLC.

[0035] Add 25.3 g of resorcinol and 40.0 g of potassium dihydrogen phosphate to the above reaction bottle, irradiate the reaction bottle with a 36W CFL, and stir the reaction at room temperature for 14 hours. Filter the reaction solution, concentrate the filtrate under reduced pressure to about 10 mL, add 360 g of saturated ammonium chloride aqueous solution, precipitate a yellow solid, filter, and wash the filter cake with 100 mL of water until the pH value of the filtrate is 6. The obtained solid was dried under reduced pressure at 50-60 ° C to obtain 35.1 g of yellow powder, with a yield of 87% and a purity of 98.5% detected by HPLC.

[0036] The present invention conducted a nuclear magnetic resonance test on the 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine prepared in Example 1 using a nuclear magnetic resonance spectrometer (model: Bruker 400 MHz). Figure 1 The 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine prepared in Example 1 is 1 H NMR spectrum, spectrum information is:

[0037] 1 H NMR (400 MHz, d 6 -DMSO): δ 13.15 (br, 2 H, OH), 10.48 (br, 2 H, OH), 8.20–8.35 (m, 4 H, Ar), 7.16 (d, J = 8.0 Hz, 2 H, Ar), 6.49–6.52 (m, 2 H, Ar), 6.37 (s, 2 H, Ar), 3.88(s, 3 H, OMe).

[0038] Figure 2 The 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine prepared in Example 1 is 13 C NMR spectrum, spectrum information is:

[0039] 13 C NMR (101 MHz, d 6 -DMSO): δ 169.6 (s, Ar), 167.6 (s, Ar), 164.7 (s, Ar), 164.2 (s, Ar), 164.1 (s, Ar), 131.7 (s, Ar), 130.7 (s, Ar), 126.6 (s, Ar), 115.1 (s, Ar), 109.3(s, Ar), 109.2(s, Ar), 103.6(s, Ar), 56.1(s, OMe).

[0040] Figure 3 It is the infrared spectrum of UVT-150 synthesized by the method of Example 1 of the present invention. Figure 3 Middle 3290 cm -1 The broad peak at 2938-3013 cm is the stretching vibration peak of O–H. -1 The stretching vibration absorption peak of the aromatic ring skeleton is 1503-1606cm -1 It is the stretching vibration absorption peak of the triazine ring skeleton.

[0041] The purity of the product 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine in this embodiment is 99.3%, which fully meets the requirements of synthetic intermediates. The HPLC analysis results are as follows: Figure 4 shown.

[0042] Example 2

[0043] In air, 18.4 g of cyanuric chloride, 11.9 g of anisole, 3.5 g of eosin Y, 13.4 g of potassium tert-butoxide and 147 g of dimethyl sulfoxide were added to a 500 mL reaction bottle, irradiated with a 36 W CFL, and stirred at room temperature for 10 h to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution. The conversion rate was 92% detected by HPLC.

[0044] Add 25.3 g of resorcinol and 40.0 g of potassium dihydrogen phosphate to the above reaction bottle, irradiate the reaction bottle with a 36W CFL, and stir the reaction at room temperature for 18 hours. Filter the reaction solution, concentrate the filtrate under reduced pressure to about 10 mL, add 360 g of saturated ammonium chloride aqueous solution, precipitate a yellow solid, filter, and wash the filter cake with 100 mL of water until the pH value of the filtrate is 6. The obtained solid was dried under reduced pressure at 50-60 ° C to obtain 32.2 g of yellow powder, with a yield of 80%, and a purity of 98.2% detected by HPLC.

[0045] Example 3

[0046] In air, 18.4 g of cyanuric chloride, 11.9 g of anisole, 3.5 g of eosin Y, 13.4 g of potassium tert-butoxide and 70 g of 1,2-dichloroethane were added to a 500 mL reaction bottle, irradiated with a 36 W CFL, and stirred at room temperature for 8 h to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution. The conversion rate was 80% as detected by HPLC.

[0047] Add 25.3 g of resorcinol and 40 g of potassium dihydrogen phosphate to the above reaction bottle, irradiate the reaction bottle with a 36W CFL, and stir the reaction at room temperature for 12 hours. Filter the reaction solution, concentrate the filtrate to about 10 mL under reduced pressure, add 360 g of saturated ammonium chloride aqueous solution, precipitate a yellow solid, filter, and wash the filter cake with 100 mL of water until the pH value of the filtrate is 6. The obtained solid was dried under reduced pressure at 50-60 ° C to obtain 26.2 g of yellow powder, with a yield of 65% and a purity of 95.8% detected by HPLC.

[0048] Example 4

[0049] In air, 18.4 g of cyanuric chloride, 11.9 g of anisole, 3.5 g of eosin Y, 13.4 g of potassium tert-butoxide and 64 g of tetrahydrofuran were added to a 500 mL reaction bottle, irradiated with a 36 W CFL, and stirred at room temperature for 10 h to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution. The conversion rate was 85% when detected by HPLC.

[0050] Add 25.3 g of resorcinol and 31 g of sodium carbonate to the above reaction bottle, irradiate the reaction bottle with a 36W CFL, and stir the reaction at room temperature for 18 hours. Filter the reaction solution, concentrate the filtrate under reduced pressure to about 10 mL, add 360 g of saturated ammonium chloride aqueous solution, precipitate a yellow solid, filter, and wash the filter cake with 100 mL of water until the pH value of the filtrate is 6. The obtained solid was dried under reduced pressure at 50-60 ° C to obtain 29.6 g of yellow powder, with a yield of 71% and a purity of 97.2% detected by HPLC.

[0051] Example 5

[0052] In air, 18.4 g of cyanuric chloride, 11.9 g of anisole, 2.8 g of anthraquinone, 13.4 g of potassium tert-butoxide and 147 g of dimethyl sulfoxide were added to a 500 mL reaction bottle, irradiated with a 36 W CFL, and stirred at room temperature for 10 h to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution. The conversion rate was 87% when detected by HPLC.

[0053] Add 25.3 g of resorcinol and 40.0 g of potassium dihydrogen phosphate to the above reaction bottle, irradiate the reaction bottle with a 36W CFL, and stir the reaction at room temperature for 18 hours. Filter the reaction solution, concentrate the filtrate under reduced pressure to about 10 mL, add 360 g of saturated ammonium chloride aqueous solution, precipitate a yellow solid, filter, and wash the filter cake with 100 mL of water until the pH value of the filtrate is 6. The obtained solid was dried under reduced pressure at 50-60 ° C to obtain 27.4 g of yellow powder, with a yield of 68% and a purity of 96.8% detected by HPLC.

[0054] Example 6

[0055] In air, 18.4 g of cyanuric chloride, 10.8 g of anisole, 3.5 g of eosin Y, 5.2 g of sodium hydroxide and 147 g of dimethyl sulfoxide were added to a 500 mL reaction bottle, irradiated with a 36 W CFL, and stirred at room temperature for 8 h to obtain a 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution. The conversion rate was 90% as detected by HPLC.

[0056] Add 22 g of resorcinol and 40.0 g of potassium dihydrogen phosphate to the above reaction bottle, irradiate the reaction bottle with a 36W CFL, and stir the reaction at room temperature for 12 hours. Filter the reaction solution, concentrate the filtrate under reduced pressure to about 10 mL, add 360 g of saturated ammonium chloride aqueous solution, precipitate a yellow solid, filter, and wash the filter cake with 100 mL of water until the pH value of the filtrate is 6. The obtained solid was dried under reduced pressure at 50-60 ° C to obtain 32.2 g of yellow powder, with a yield of 80% and a purity of 98.0% detected by HPLC.

[0057] The protection scope of the present invention is not limited to the above-mentioned embodiments. Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the scope and spirit of the present invention. If these changes and modifications fall within the scope of the claims of the present invention and their equivalents, the present invention is intended to include these changes and modifications.

Claims

1. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy, characterized in that: The steps include: Step 1: Add anisole, cyanuric chloride, solvent, base and photocatalyst into a reaction container, and react for 6-24 hours at room temperature under CFL irradiation to obtain 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution; Step 2: adding resorcinol and a base to the 2,4-dichloro-6-(4-methoxyphenyl)-1,3,5-triazine solution obtained in step 1, and then reacting at room temperature under CFL irradiation for 6-24 hours; Step 3: Filter the reaction solution of step 2, concentrate the filtrate under reduced pressure, add saturated aqueous ammonium chloride solution, precipitate solid, filter, wash the filter cake with water, and dry at 40-100° C. to obtain 2,6-(2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1,3,5-triazine; The photocatalyst in step 1 is eosin Y or anthraquinone.

2. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: In step 1, the irradiation intensity of the CFL lamp is 32-36W.

3. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: In the step 1, the molar ratio of cyanuric chloride to anisole is 1:1.1-1:1.2; the molar ratio of the photocatalyst to cyanuric chloride is 1:20-1:17; the solvent is dimethyl sulfoxide, acetonitrile, tetrahydrofuran or 1,2-dichloroethane; the mass ratio of the solvent to cyanuric chloride is 7:1-9:1; the base is sodium hydroxide, potassium hydroxide, potassium tert-butoxide or sodium tert-butoxide; the molar ratio of the base to cyanuric chloride is 1:1.2-1:1.

3.

4. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: The specific reaction time of step 1 is determined according to the conversion rate detected by the central control. After 4 hours of reaction, sampling and monitoring are carried out every hour. When the conversion rate does not increase, the reaction is stopped.

5. The method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: In step 2, the irradiation intensity of the CFL lamp is 32-36W.

6. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: In the step 2, the molar ratio of resorcinol to cyanuric chloride added in the step 1 is 2.1:1-2.2:1; the base is dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate or triethylamine; and the molar ratio of the base to resorcinol is 2.2:1-2.4:

1.

7. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: The specific reaction time of step 2 is determined according to the conversion rate detected by the central control. After 4 hours of reaction, sampling and monitoring are carried out every hour. When the conversion rate does not increase, the reaction is stopped.

8. A method for synthesizing a key intermediate of ultraviolet absorber UV-627 based on a photocatalytic strategy as claimed in claim 1, characterized in that: The filtrate in step 3 is concentrated under reduced pressure to 5-10% of the original volume; a saturated aqueous ammonium chloride solution is added with a mass ratio of 18:1-23:1 to the cyanuric chloride added in step 1; and the product is dried at 50-60°C.

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