A method for synthesizing ultraviolet absorber HEB based on copper photocatalytic strategy

Abstract

The application provides a method for synthesizing triazine ultraviolet absorber HEB based on a copper photocatalysis strategy, and adopts the photocatalysis strategy to efficiently synthesize the ultraviolet absorber HEB at room temperature, and the method comprises the following steps: under the irradiation of blue light at room temperature, melamine and 4-chloro-N-tert-butyl benzamide are photocatalyzed by copper to obtain N-tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino] benzamide solution; 4-chlorobenzoic acid isooctyl ester and alkali are added, and the mixture is reacted under the irradiation of blue light at room temperature; the reaction solution is filtered, water and ethyl acetate are added, and the mixture is separated; the organic phase is dried with anhydrous magnesium sulfate, and then activated carbon is added into the filtered solution to heat and reflux; then, the mixture is cooled to room temperature and filtered, the solvent is removed from the filtrate through reduced pressure distillation, and then the crude product is obtained; finally, the product HEB is obtained through recrystallization of the crude product with ethanol and water. The method has the advantages of mild reaction conditions, simple operation, low energy consumption and high product purity.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing triazine ultraviolet absorber HEB based on a copper photocatalysis strategy. BACKGROUND

[0002] Ultraviolet absorber HEB, also known as diethylhexyl butyramido triazone, belongs to 1,3,5-triazine ultraviolet absorber series products, has a wavelength absorption range of 280-380 nm, an absorption peak of 311 nm, good light stability, good thermal stability, high absorption efficiency, low toxicity and the like, and good compatibility with oil and fat ingredients, can be used in various sunscreen products, and a general dosage is 0.5-2%. HEB can efficiently and widely absorb UV-A and UV-B band ultraviolet rays, and has been approved by the United States, the European Union, Australia and Japan to be applied to the sunscreen and skin care industries.

[0003] At present, there are mainly three methods for preparing HEB at home and abroad.

[0004] Method one: US patent applications with publication numbers US05346691 and US20130280190 use 4-nitrobenzoic acid as a starting material, and sequentially react with dichlorosulfoxide, t-butylamine and Raney nickel through three steps to obtain 4-amino-N-t-butylbenzamide, and then the 4-amino-N-t-butylbenzamide reacts with cyanuric chloride to obtain N-t-butyl-4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzamide, and then the N-t-butyl-4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzamide reacts with 4-aminobenzoic acid isooctyl ester to obtain HEB. On this basis, the Chinese invention patent application with publication number CN105130918 directly uses 4-amino-N-t-butylbenzamide as a starting material, and first reacts with cyanuric chloride to obtain N-t-butyl-4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzamide, and then the N-t-butyl-4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzamide reacts with 4-aminobenzoic acid isooctyl ester to obtain HEB. The chemical reaction equation of the method is shown as follows:

[0005]

[0006] Method two: the US patent application with publication number US20130281692 uses 4-nitrobenzoic acid and cyanuric chloride as starting materials, first performs a substitution reaction, and then sequentially reacts with 4-aminobenzoic acid isooctyl ester, dichlorosulfoxide and t-butylamine to obtain HEB. The chemical reaction equation of the method is shown as follows:

[0007]

[0008] The above two methods have long synthetic process route, complex operation and high cost. Due to the high activity of cyanuric chloride, a small amount of disubstituted or even trisubstituted products will be generated when reacting with 4-amino-N-tert-butyl benzamide or 4-amino-N-tert-butyl benzoic acid, resulting in difficult product refining.

[0009] Method three: Chinese invention patent application No. CN110229113 selects melamine, 4-chloro-N-tert-butyl benzamide and 4-chlorobenzoic acid isooctyl ester as raw materials, and adopts two-step one-pot method to efficiently prepare HEB. However, the reaction temperature of the method is relatively high, 90-120℃, the reaction time is long, 40-46h, and the energy consumption is very large. In addition, due to the low activity of chloroarene, the reaction is incomplete, which increases the difficulty of separation and purification of the product, resulting in low yield. The chemical reaction equation of the method is shown in the following formula:

[0010]

[0011] Light is an easily available and green energy. In the past two decades, photo-oxidation and reduction catalytic reactions have been widely used in organic synthesis as a new and efficient catalytic strategy. (Chem. Rev. 2013, 113, 5322; Acc. Chem. Res. 2016, 49, 1557; Acc. Chem. Res. 2016, 49, 1990.) Compared with traditional synthesis strategies, photo-catalytic strategies can efficiently construct C–N bonds under milder reaction conditions. SUMMARY

[0012] In view of the problems existing in the prior art, the present application provides a method for synthesizing triazine ultraviolet absorber HEB based on copper photo-catalytic strategy, which has the advantages of simple operation, mild reaction conditions, high yield and high product purity. The technical solutions adopted by the present application to solve the problems existing in the prior art are as follows:

[0013] A method for synthesizing triazine ultraviolet absorber HEB based on copper photo-catalytic strategy, comprising the following steps:

[0014] Step 1: adding melamine, 4-chloro-N-tert-butyl benzamide, a solvent, a base and a photocatalyst into a reaction container, and reacting at room temperature under blue light irradiation for 4-10h to obtain a N-tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino] benzamide solution;

[0015] Step 2: adding 4-chlorobenzoic acid isooctyl ester and a base to the N-tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino] benzamide solution obtained in step 1, and then reacting at room temperature under blue light irradiation for 6-12h;

[0016] Step 3: add water and ethyl acetate to the reaction solution of step 2, separate the liquid, dry the organic phase with anhydrous magnesium sulfate, filter the filtrate, add decolorizing agent activated carbon to the filtrate and heat to reflux for 1 h, then cool to room temperature, filter, and remove the solvent by distillation under reduced pressure to obtain the crude product, which is recrystallized with ethanol and water to obtain the product HEB.

[0017] The chemical structural formula of the obtained HEB is as follows:

[0018]

[0019] The reaction equation of the method of the present application is shown as follows:

[0020]

[0021] The photocatalyst in step 1 is one of copper salts, preferably, the photocatalyst comprises CuCl, CuI, [Cu(CH3CN)4]PF6 or [Cu(phen)2]Cl, wherein phen = 1,10-phenanthroline, and the photocatalyst has a great influence on the conversion rate of the reaction.

[0022] The solvent in step 1 is one of dimethyl sulfoxide, N,N-dimethylformamide, toluene and acetonitrile, and preferably the solvent is dimethyl sulfoxide.

[0023] The base in steps 1 and 2 is one of sodium salts, preferably sodium hydroxide, sodium tert-butoxide, sodium methoxide or sodium carbonate, and the selection of the base directly affects the efficiency of the reaction.

[0024] The light source in steps 1 and 2 is visible light, preferably blue light, and the irradiation intensity of the blue light is 24-64 W, and the preferred irradiation intensity is 48 W, and the intensity of the light affects the efficiency of the reaction.

[0025] In step 1, the molar ratio of melamine to 4-chloro-N-tert-butyl benzoyl is 1:1.0-1:1.2, and the preferred molar ratio is 1:1.05-1:1.1; the molar ratio of the photocatalyst to melamine is 1:200-1:20, and the preferred molar ratio is 1:100-1:90; the mass ratio of the solvent to melamine is 1:1-10:1, and the preferred mass ratio is 3:1-5:1, and too little solvent will make stirring difficult; the molar ratio of the base to cyanuric chloride is 1.0:1-1.5:1, and the preferred molar ratio is 1.1:1-1.2:1. The specific reaction time is determined according to the conversion rate monitored by the central control, the reaction is stopped when the conversion rate does not increase after 4 h, the reaction time is 4-10 h, and the preferred reaction time is 6-8 h.

[0026] The molar ratio of 4-chlorobenzoic acid isooctyl ester in step 2 to melamine in step 1 is 2.1:1-2.4:1, preferably 2.1:1-2.2:1; the molar ratio of the base to melamine is 2.0:1-4.0:1, preferably 2.3:1-2.5:1. The specific reaction time is determined according to the conversion rate of the intermediate control, and the reaction is stopped when the conversion rate does not increase after 4 hours, the reaction time is 6-12 hours, preferably 8-10 hours.

[0027] The mass ratio of water added in step 3 to cyanuric chloride in step 1 is 2:1-5:1, preferably 2:1-3:1; the mass ratio of ethyl acetate to cyanuric chloride in step 1 is 1:1-4:1, preferably 2:1-3:1; the mass ratio of activated carbon to cyanuric chloride is 1:5-1:20, preferably 1:9-1:10; in the recrystallization experiment, the mass ratio of ethanol to 4-chlorobenzoic acid is 1:2-3:1, preferably 1:1-1:1.5; the mass ratio of ethanol to water is 1:5-1:20, preferably 1:9-1:10.

[0028] The present application has the following advantages:

[0029] (1) Compared with the traditional synthesis strategy, the method of the present application has mild reaction conditions, short reaction time and low energy consumption.

[0030] (2) The intermediate N-tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino]benzamide does not need to be separated and purified, and can be directly used for the next reaction, thereby reducing the operation process, reducing the production cost and equipment investment.

[0031] (3) The present application uses a cheap copper salt as a photocatalyst, the catalyst consumption is low, the product yield is high, and the product purity is greater than 99%. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 The HEB prepared in Example 1 1 H NMR spectrum;

[0033] Figure 2 The HEB prepared in Example 1 13 C NMR spectrum;

[0034] Figure 3 The infrared spectrum of the HEB synthesized by the method of Example 1 of the present application;

[0035] Figure 4 The liquid chromatogram of the HEB synthesized in Example 1 of the present application. DETAILED DESCRIPTION

[0036] The technical solutions of the present application are further specifically described below by examples in combination with the drawings.

[0037] Example 1

[0038] Into a 250 mL reaction flask, 12.6 g of cyanuric chloride, 21.1 g of 4-chloro-N-tert-butyl benzamide, 0.25 g of [Cu(phen)2]Cl, 4.5 g of sodium hydroxide and 23.5 g of dimethyl sulfoxide were added, the reaction flask was irradiated with 48 W blue light, and the reaction was stirred at room temperature for 8 h to obtain a N-tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino] benzamide solution, and the conversion rate was 98% detected by HPLC.

[0039] Into the above reaction flask, 56.5 g of 4-chlorobenzoic acid isooctyl ester and 9.5 g of sodium hydroxide were added, the reaction flask was irradiated with 48 W blue light, and the reaction was stirred at room temperature for 10 h. 35 g of water and 26 g of ethyl acetate were added, the liquid was separated, 1.3 g of decolorizing agent activated carbon was added to the organic phase, heated to reflux for 1 h, cooled, filtered, and the filtrate was distilled under reduced pressure to obtain a crude product, which was recrystallized with 13 g of ethanol and 120 g of water to obtain 71.6 g of product HEB, with a yield of 93.5% and a purity of 99.5% detected by HPLC.

[0040] The HEB prepared in Example 1 was subjected to nuclear magnetic testing by a nuclear magnetic spectrometer (model: Bruker 400 MHz), Figure 1 The HEB prepared in Example 1 was subjected to nuclear magnetic testing by a nuclear magnetic spectrometer (model: Bruker 400 MHz), 1 The H NMR spectrum is as follows: 1 H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8.6 Hz, 4 H, Ar), 7.57-7.76 (m, 8 H, Ar), 7.36 (br, 2H, NH), 7.31 (br, 1 H, NH), 5.94 (br, 1 H, NH), 4.18-4.29 (m, 4 H, OCH2), 1.68-1.77 (m, 2 H, alkyl-H), 1.49 (s, 9 H, CMe3), 1.29-1.48 (m, 16 H, alkyl-H), 0.87-0.98 (m, 12 H, Me).

[0041] Figure 2 The HEB prepared in Example 1 was subjected to nuclear magnetic testing by a nuclear magnetic spectrometer (model: Bruker 400 MHz), 13 The C NMR spectrum is as follows: 13C NMR (101 MHz, CDCl3): δ 166.4 (s, COO), 166.3 (s, CON), 142.5 (s, Ar), 140.9 (s, Ar), 130.7 (s, Ar), 127.7 (s, Ar), 125.2 (s, Ar), 119.7 (s, Ar), 119.4 (s, Ar), 67.3 (s,OCH2CH), 51.6 (s, CMe3), 39.0 (s, OCH2CH), 30.6 (s, CH2), 29.0 (s, CH2), 29.0 (s, CH2), 24.0 (s, CH2), 23.0 (s, CMe3), 14.1 (s, Me), 11.1 (s, Me).

[0042] Figure 3 This is the infrared spectrum of HEB synthesized by the method in Example 1 of this invention. Figure 3 It can be determined that: 3185-3292 cm -1 The peaks represent the stretching vibrations of N–H, 2928–2958 cm⁻¹. -1 The absorption peaks are due to the stretching vibrations of the aromatic ring skeleton, 1697-1720 cm⁻¹. -1 The peak at 1414-1573 cm⁻¹ is the characteristic absorption peak of the carbonyl group. -1 The absorption peaks are due to the stretching vibrations of the triazine ring skeleton, ranging from 1108 to 1272 cm⁻¹. -1 This is a characteristic absorption peak for C–O–C in esters.

[0043] The HEB purity of the product in this implementation plan is 99.5%, which fully meets the requirements of the cosmetics industry. HPLC analysis results are as follows: Figure 4 As shown.

[0044] Example 2

[0045] 12.6 g of cyanuric chloride, 21.1 g of 4-chloro-N-tert-butylbenzoyl, 0.2 g of CuI, 4.5 g of sodium hydroxide, and 23.5 g of dimethyl sulfoxide were added to a 250 mL reaction flask. The reaction flask was irradiated with 48 W blue light and stirred at room temperature for 8 h to obtain an N-tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino]benzamide solution. The conversion rate was 92% as determined by HPLC.

[0046] To the above reaction flask, 56.5 g of 4-chlorobenzoic acid isooctyl ester and 9.5 g of sodium hydroxide were added, the reaction flask was irradiated with 48W blue light, and the reaction was stirred at room temperature for 10 h. 35 g of water and 26 g of ethyl acetate were added, and the organic phase was added with 1.3 g of decolorizing agent activated carbon and heated to reflux for 1 h, cooled, filtered, and the filtrate was distilled under reduced pressure to obtain a crude product, which was recrystallized with 13 g of ethanol and 120 g of water to obtain 68.2 g of product HEB, with a yield of 89% and a purity of 98.7% detected by HPLC.

[0047] Example 3

[0048] To the above reaction flask, 56.5 g of 4-chlorobenzoic acid isooctyl ester and 9.5 g of sodium hydroxide were added, the reaction flask was irradiated with 48W blue light, and the reaction was stirred at room temperature for 10 h. 35 g of water and 26 g of ethyl acetate were added, and the organic phase was added with 1.3 g of decolorizing agent activated carbon and heated to reflux for 1 h, cooled, filtered, and the filtrate was distilled under reduced pressure to obtain a crude product, which was recrystallized with 13 g of ethanol and 120 g of water to obtain 68.2 g of product HEB, with a yield of 89% and a purity of 98.7% detected by HPLC.

[0049] To the above reaction flask, 56.5 g of 4-chlorobenzoic acid isooctyl ester and 9.5 g of sodium hydroxide were added, the reaction flask was irradiated with 48W blue light, and the reaction was stirred at room temperature for 10 h. 35 g of water and 26 g of ethyl acetate were added, and the organic phase was added with 1.3 g of decolorizing agent activated carbon and heated to reflux for 1 h, cooled, filtered, and the filtrate was distilled under reduced pressure to obtain a crude product, which was recrystallized with 13 g of ethanol and 120 g of water to obtain 68.2 g of product HEB, with a yield of 89% and a purity of 98.7% detected by HPLC.

[0050] The scope of protection of the present application is not limited to the above-mentioned examples, and it is obvious that those skilled in the art can make various modifications and changes to the present application without departing from the scope and spirit of the present application. If these modifications and changes fall within the scope of the claims of the present application and their equivalent technologies, the intention of the present application also includes these modifications and changes.

Claims

1. A method for synthesizing triazine-based ultraviolet absorber HEB based on copper photocatalytic strategy, characterized in that, Comprising the following steps: Step 1 : Melamine, 4-chloro-3-nitrophenol, solvent, base and a photocatalyst were added to a reaction vessel and reacted at room temperature under blue light irradiation for 4-10 h to obtain N -tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino]benzamide solution N -tert-butyl-4-[(4,6-diamino-1,3,5-triazin-2-yl)amino]benzamide solution Step 2: To the solution of Step 1 N - t-butyl-4-[(4,6-diamino-l,3,5-triazin-2-yl)amino]benzamide solution is added isooctyl 4-chlorobenzoate and base, followed by reaction under blue light irradiation at room temperature for 6-12 h; Step 3: adding water and ethyl acetate to the reaction solution obtained in step 2, separating the liquid, drying the organic phase with anhydrous magnesium sulfate, adding decolorizing agent activated carbon to the filtrate after filtration, heating to reflux for 1 h, then cooling to room temperature and filtering, removing the solvent by distillation under reduced pressure to obtain a crude product, and recrystallizing with ethanol and water to obtain the product HEB; The photocatalyst in step 1 is one of copper salts, the solvent in step 1 is dimethyl sulfoxide, N , N one of dimethylformamide, toluene and acetonitrile, the base in step 1 is one of sodium salts, the irradiation light source in step 1 is blue light, the irradiation intensity of blue light is 24-64 W, the base in step 2 is one of sodium salts, the irradiation light source in step 2 is blue light; the irradiation intensity of blue light is 24-64 W.

2. A method for synthesis of triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The photocatalyst in step 1 is one of CuCl, CuI, [Cu(CH3CN)4]PF6 or [Cu(phen)2]Cl, wherein phen = 1,10-phenanthroline.

3. A method of synthesizing triazine-based ultraviolet absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The solvent in step 1 is dimethyl sulfoxide.

4. A method of synthesizing triazine-based ultraviolet absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The base in step 1 is one of sodium hydroxide, sodium tert-butoxide, sodium methoxide or sodium carbonate.

5. A method of synthesizing triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The irradiation intensity of blue light irradiation in step 1 is 48 W.

6. A method of synthesizing triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: the molar ratio of melamine to 4-chloro- N 1:1.05-1:1.1; the molar ratio of photocatalyst to melamine is 1:100-1:90; the mass ratio of solvent to melamine is 3:1-5:1; the molar ratio of base to cyanuric chloride is 1.1:1-1.2:1, and the specific reaction time of step 1 is determined according to the conversion rate monitored by the central control, and the reaction is stopped when the conversion rate does not increase after 4 hours.

7. A method of synthesizing triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The base in step 2 is one of sodium hydroxide, sodium tert-butoxide, sodium methoxide or sodium carbonate.

8. A method of synthesizing triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The irradiation intensity of blue light irradiation in step 2 is 48 W.

9. A method of synthesizing triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The molar ratio of 4-chlorobenzoic acid isooctyl ester in step 2 to the melamine put in step 1 is 2.1:1-2.2:1; the molar ratio of the base to the melamine is 2.3:1-2.5:1, and the specific reaction time is determined according to the conversion rate monitored every hour after 4 h of reaction, and the reaction is stopped when the conversion rate does not increase.

10. A method of synthesizing triazine-based UV absorber HEB based on copper photocatalytic strategy according to claim 1, characterized in that: The mass ratio of water added in step 3 to the cyanuric chloride put in step 1 is 2:1-3:1; the mass ratio of ethyl acetate to the cyanuric chloride put in step 1 is 2:1-3:1; the mass ratio of activated carbon to the cyanuric chloride is 1:9-1:10; in the recrystallization experiment, the mass ratio of ethanol to 4-chlorobenzoic acid is 1:1-1:1.5; and the mass ratio of ethanol to water is 1:9-1:10.

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