Preparation method of ultraviolet absorbent HEB

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of an ultraviolet absorbent HEB. The invention provides a preparation method of an ultraviolet absorbent HEB. The preparation method comprises the following steps: firstly, reacting cyanuric chloride with para aminobenzoic acid under an alkaline condition to obtain an intermediate A; reacting the obtained intermediate A with tert-butylamine to obtain an intermediate B; and finally, reacting the intermediate B with 2-ethylhexyl acetate under an alkaline condition, and carrying out subsequent treatment to obtain the ultraviolet absorbent HEB. The preparation method of the ultraviolet absorbent HEB is mild in reaction condition, simple in process operation and low in energy consumption, the used raw materials are high in reaction activity, few in side reaction and low in cost, the obtained intermediate product is stable and high in purity, and large-scale production is facilitated.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of an ultraviolet absorber HEB. Background Art

[0002] HEB, also known as diethylhexyl butamido triazone, is a new type of triazine ultraviolet absorber, with the chemical name of bis(2-ethylhexyl)-4,4'-((6-((4-tert-butylaminocarbonyl)phenyl)amino)-1,3,5-triazine-2,4-diyl)diimino)dibenzoate. It has a relatively high absorption efficiency for ultraviolet rays, can absorb ultraviolet rays in both UVA (275 - 320 nm) and UVB (320 - 400 nm) bands simultaneously, has good light stability and thermal stability as well as good broad-spectrum sunscreen effect, and has currently been applied to sunscreens in countries such as the United States, the European Union, and Japan. Currently, the preparation methods of HEB reported at home and abroad mainly include the following three:

[0003] Method 1: Using cyanuric chloride as a raw material, reacting cyanuric chloride with N-tert-butyl-4-aminobenzamide to obtain N-tert-butyl-4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzamide, and then reacting the latter with isooctyl 4-aminobenzoate to prepare diethylhexyl butamido triazone HEB, as specifically shown in Reaction Route I.

[0004]

[0005] Method 2: Preparing diethylhexyl butamido triazone HEB by four-step reactions of cyanuric chloride with p-aminobenzoic acid, isooctyl 4-aminobenzoate, thionyl chloride, and tert-butylamine in sequence, as specifically shown in Reaction Route II.

[0006]

[0007] Method 3: Using melamine, N-tert-butyl-4-chlorobenzamide, and isooctyl 4-chlorobenzoate as raw materials, and preparing diethylhexyl butamido triazone HEB by a one-pot reaction, as specifically shown in Reaction Route III.

[0008]

[0009] However, each of the above three methods has certain defects. For example, although both Method 1 and Method 2 use cyanuric chloride as the raw material, the intermediate products obtained are unstable in air and easily decompose when exposed to water. Moreover, the first-step reactions of Method 1 and Method 2 both involve the reaction of highly reactive cyanuric chloride with aromatic primary amines, and it is difficult to stop this reaction at only forming the monoamino-substituted triazine intermediates N-tert-butyl-4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzamide (Method 1) and 4-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]benzoic acid (Method 2). It is easy to generate a small amount of diamino-substituted and triamino-substituted impurity products, and the generation of these impurity products makes the subsequent purification process more complicated. In addition, the monoamino-substituted triazine intermediate is extremely easy to react with water vapor in the air, resulting in poor storage stability of the intermediate, and more stringent industrial production conditions are required to meet the storage requirements. Although Method 3 avoids the problems of Method 1 and Method 2, the required reaction time is long and the energy consumption is high, which does not conform to the green and environmental protection production concept. Moreover, some of the raw materials used in the above three methods are expensive, increasing the production cost. Summary of the Invention

[0010] In view of this, the present invention provides a preparation method of ultraviolet absorber HEB. The preparation method has mild reaction conditions, simple process operation, low energy consumption, high reaction activity of the raw materials used, few side reactions, low cost, and the obtained intermediate products are stable and have high purity, which is conducive to realizing large-scale production.

[0011] To solve the above technical problems, the first aspect of the present invention provides a preparation method of ultraviolet absorber HEB, and the steps include:

[0012] S1. Add a second solution dissolved with p-aminobenzoic acid dropwise to a first solution dissolved with cyanuric chloride and a basic reagent at 0-20°C to allow p-aminobenzoic acid to substitute for 3 chlorine atoms on cyanuric chloride, and separate to obtain intermediate A;

[0013] S2. Add the intermediate A and tert-butylamine to 200# solvent oil, and react the intermediate A and tert-butylamine at 160-180°C for 3-5 h. After the reaction is completed, perform solid-liquid separation and collect the solid to obtain intermediate B;

[0014] S3. Add the intermediate B, 2-ethylhexyl acetate and a basic reagent to an organic solvent, react at 110-130°C for 5-7 h, cool to room temperature after the reaction is completed, wash with water, collect the organic phase, remove the organic solvent, and perform recrystallization to obtain ultraviolet absorber HEB.

[0015] In the present invention, cyanuric chloride and p-aminobenzoic acid are used as raw materials to react to obtain intermediate A. In this process, all three chlorine atoms in cyanuric chloride react with p-aminobenzoic acid, solving the problem that the existing reaction route requires precise control of the reaction sites. Moreover, the obtained intermediate A has better stability, can be stored stably for a long time and does not react with water vapor in the air. The obtained intermediate A is reacted with tert-butylamine. After 1 molecule of intermediate A reacts with 1 molecule of tert-butylamine, intermediate B, which is insoluble in the solvent, is formed. The sharp change in solubility causes intermediate B to rapidly precipitate from the solution, avoiding the continuous reaction of intermediate B with tert-butylamine, that is, avoiding the side reactions of disubstitution or trisubstitution of intermediate A, and simplifying the subsequent reaction steps and purification process. The obtained intermediate B is reacted with 2-ethylhexyl acetate under alkaline conditions, and after washing with water, the organic solvent is removed and the HEB crude product is precipitated.

[0016] The reaction principle of the preparation method provided by the present invention is as follows:

[0017]

[0018] Combined with the first aspect, in step S1, the molar ratios of cyanuric chloride, p-aminobenzoic acid and the basic reagent are 1:3.1 - 3.3:1.1 - 1.3 in sequence, preferably 1:3.15:1.2.

[0019] Combined with the first aspect, in step S1, the solvents in the first solution and the second solution are the same, both being acetonitrile or acetone.

[0020] Combined with the first aspect, in step S2, the molar ratio of intermediate A to tert-butylamine is 1:1.04 - 1.1, preferably 1:1.05.

[0021] Combined with the first aspect, in step S2, the solvent is 200# solvent oil. 200# solvent oil is a slightly yellowish liquid, composed of petroleum fractions at 140 - 200 °C, and is prepared by pretreatment and atmospheric distillation of petroleum.

[0022] Combined with the first aspect, in step S2, each gram of intermediate A is dissolved in 3 - 8 mL of the 200# solvent oil.

[0023] Combined with the first aspect, in step S3, the molar ratios of intermediate B, 2-ethylhexyl acetate and the basic reagent are 1:3.5 - 5:0.05 - 0.1 in sequence, preferably 1:4 - 4.43:0.06 - 0.08, and further preferably 1:4.3:0.076.

[0024] Combined with the first aspect, in step S3, the organic solvent is toluene or xylene.

[0025] In combination with the first aspect, in step S3, each gram of the intermediate B is dissolved in 3 to 6 mL of the toluene.

[0026] In combination with the first aspect, the basic reagent is selected from any one of sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and potassium methoxide.

[0027] Preferably, the basic reagent in step S1 is preferably sodium bicarbonate, and the basic reagent in step S3 is preferably potassium methoxide.

[0028] In combination with the first aspect, in step S3, a mixed solution of ethanol and water is used to recrystallize the obtained solid.

[0029] When recrystallization is carried out, the volume ratio of ethanol to water is 10:0.5 to 2, preferably 10:1.

[0030] The second aspect of the present invention provides an ultraviolet absorber HEB, which is prepared according to the above preparation method. The purity of the obtained ultraviolet absorber HEB can reach more than 98%.

[0031] The beneficial effects of the present invention: In the preparation method of the ultraviolet absorber HEB provided by the present invention, the raw materials used are all common industrial raw materials, which are low in price and easy to obtain. Moreover, intermediate A and intermediate B do not require complex purification steps during the preparation process and have good storage stability. In addition, the reaction raw materials used in the present invention all have high reaction activity, shortening the reaction time, thereby reducing the energy consumption during the production process. Furthermore, the above reaction route provided by the present invention is simple in process, more environmentally friendly, and the organic solvents used are easy to recycle and reuse, with low production costs and suitable for large-scale production. Description of the Drawings

[0032] Figure 1 It is the high-performance liquid chromatography diagram of the ultraviolet absorption and HEB obtained in Example 1 of the present invention. Detailed Embodiments

[0033] In order to make the objectives, technical solutions, and advantages of the present invention clearer, the following further describes the present invention in detail with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0034] Most of the current preparation methods of diethylhexyl butamido triazone (HEB) have problems such as poor stability of intermediate products, many side reactions, cumbersome post-treatment steps, high cost of reaction raw materials, harsh reaction conditions, and high energy consumption. In view of this, the present invention provides a new preparation method of the ultraviolet absorber HEB. The preparation route of this method is simple, the reaction conditions are mild, the process operation is convenient, the production energy consumption is greatly reduced, and the reaction activity of the raw materials used in this method is high, the side reactions are few, the cost is low, the obtained intermediate products are stable and have high purity, and there is no need for harsh reaction conditions to ensure the stability of the intermediate products. The yield and purity of the final product HEB are high, with significant technical advantages and economic benefits.

[0035] The following specifically describes the preparation method of the ultraviolet absorber HEB provided by the present invention through specific examples.

[0036] The reaction reagents and equipment used in the present invention are all conventional commercially available ordinary reagents and ordinary equipment.

[0037] In the following examples, the detection conditions of the high performance liquid chromatography used are as follows:

[0038] Model of liquid chromatograph: Agilent 1260 Infinity; Detector: DAD; Model of chromatographic column: ZORBAX SB-C18; Specification of chromatographic column: 4.6×150 mm, 5 μm; Detection wavelength: 307 nm; Mobile phase: water: methanol = 2:98; Flow rate of mobile phase: 1 mL / min; Injection volume: 0.5 mL; Preparation of injection solution: Dissolve 5.25 mg of the sample to be detected in 10 mL of methanol of chromatographic grade.

[0039] Example 1

[0040] This example provides a preparation method of the ultraviolet absorber HEB, and the specific steps include:

[0041] S1. Put 138.3 g (0.75 mol) of cyanuric chloride, 75.6 g (0.90 mol) of sodium bicarbonate and 300 mL of acetonitrile into the reactor, control the reaction temperature at 10 °C, stir and dissolve, and slowly dropwise add a 500 mL acetonitrile solution containing 323.99 g (2.36 mol) of p-aminobenzoic acid at this temperature. Finish dropping within 3 - 4 h, then keep the reaction at 10 °C for 2 h. After the reaction is completed, remove the solvent by reduced pressure to obtain intermediate A;

[0042] S2. Take 200 g (0.41 mol) of the above-obtained intermediate A, put it into the reactor, then add 600 mL of 200# solvent oil and 33.20 g (0.45 mol) of tert-butylamine to it, control the reaction temperature at 170 °C, control the reaction time at 4 h, and filter after stopping the reaction to obtain intermediate B;

[0043] S3. Take 200 g (0.37 mol) of the above-mentioned intermediate B and put it into a reactor. Then add 274.24 g (1.59 mol) of 2-ethylhexyl acetate, 600 mL of toluene, and 1.95 g (0.028 mol) of potassium methoxide. After the feeding is completed, raise the temperature to 110 °C and continue the reaction at this temperature for 6 h. After the reaction is completed, cool it to room temperature, wash it with water, separate the lower aqueous layer by liquid separation, remove the excess organic solvent by rotary evaporation to obtain the crude product of the target product HEB, and then recrystallize it with a mixed solution of ethanol and water (volume ratio 10:1) to obtain high-purity HEB.

[0044] After calculation, the total yield of the above three-step reaction is greater than 89%. The chemical structure of the obtained final product HEB was confirmed by nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum analysis. Its purity was detected by liquid chromatography to be 98.62% (corresponding to peak 11 in the following table, and the peak area is 98.62% with two decimal places reserved). The liquid chromatogram is as Figure 1 shown, and the result analysis is shown in the following table:

[0045]

[0046] Example 2

[0047] This example provides a preparation method of the ultraviolet absorber HEB, and the specific steps include:

[0048] S1. Put 138.3 g (0.75 mol) of cyanuric chloride, 81.9 g (0.97 mol) of sodium bicarbonate, and 300 mL of acetone into a reactor. Control the reaction temperature at 5 °C and stir to dissolve. Slowly dropwise add a 500 mL acetone solution containing 323.99 g (2.36 mol) of p-aminobenzoic acid at this temperature, and finish the dropping within 3 - 4 h. Then keep the temperature at 5 °C and react for 2 h. After the reaction is completed, remove the solvent by reduced pressure to obtain intermediate A;

[0049] S2. Take 200 g (0.41 mol) of the above-mentioned intermediate A and put it into a reactor. Then add 600 mL of 200# solvent oil and 33.20 g (0.45 mol) of tert-butylamine. Control the reaction temperature at 165 °C and the reaction time at 4.5 h. Stop the reaction and cool it to 0 °C, and the product will precipitate. Then filter to obtain intermediate B;

[0050] S3. Take 200 g (0.37 mol) of the intermediate B obtained above and put it into a reactor. Then add 274.24 g (1.59 mol) of 2-ethylhexyl acetate, 600 mL of toluene, and 1.95 g (0.028 mol) of potassium methoxide. After feeding, heat up to 110 °C and continue to react at this temperature for 6.5 h. After the reaction is completed, cool to room temperature, wash with water and then separate the lower aqueous layer by liquid separation. Remove the excess organic solvent by rotary evaporation to obtain the crude product of the target product HEB. Then recrystallize with a mixed solution of ethanol and water (10:1) to obtain high-purity HEB.

[0051] Calculated, the total yield of the three-step reaction is greater than 89%. The chemical structure of the obtained final product HEB was confirmed by nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum analysis. Its purity was detected by liquid chromatography to be 97.52%.

[0052] Example 3

[0053] This example provides a preparation method of the ultraviolet absorber HEB. The specific steps include:

[0054] S1. Put 138.3 g (0.75 mol) of cyanuric chloride, 75.6 g (0.90 mol) of sodium bicarbonate, and 300 mL of acetonitrile into a reactor. Control the reaction temperature at 0 °C, stir and dissolve. Slowly dropwise add a 400 mL acetonitrile solution containing 323.99 g (2.36 mol) of p-aminobenzoic acid at this temperature, and finish dropping within 3 - 4 h. Then keep the temperature at 0 °C for 2 h for the reaction. After the reaction is completed, remove the solvent by reduced pressure to obtain intermediate A.

[0055] S2. Take 200 g (0.41 mol) of the intermediate A obtained above and put it into a reactor. Then add 600 mL of 200# solvent oil and 33.20 g (0.45 mol) of tert-butylamine. Control the reaction temperature at 160 °C and the reaction time at 5 h. Stop the reaction and cool to 0 °C, and the product will precipitate. Then filter to obtain intermediate B.

[0056] S3. Take 200 g (0.37 mol) of the intermediate B obtained above and put it into a reactor. Then add 274.24 g (1.59 mol) of 2-ethylhexyl acetate, 600 mL of toluene, and 1.95 g (0.028 mol) of potassium methoxide. After feeding, heat up to 110 °C and continue to react at this temperature for 7 h. After the reaction is completed, cool to room temperature, wash with water and then separate the lower aqueous layer by liquid separation. Remove the excess organic solvent by rotary evaporation to obtain the crude product of the target product HEB. Then recrystallize with a mixed solution of ethanol and water (10:1) to obtain high-purity HEB.

[0057] After calculation, the total yield of the three-step reaction is greater than 89%; the chemical structure of the obtained final product HEB was confirmed by nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum analysis, and its purity was detected by liquid chromatography to be 97.98%.

[0058] Example 4

[0059] This example provides a preparation method of the ultraviolet absorber HEB, and the specific steps include:

[0060] S1. Put 138.3 g (0.75 mol) of cyanuric chloride, 75.6 g (0.90 mol) of sodium bicarbonate and 300 mL of acetonitrile into the reactor, control the reaction temperature at 15°C, stir and dissolve, and slowly dropwise add a 400 mL acetonitrile solution containing 323.99 g (2.36 mol) of p-aminobenzoic acid at this temperature. The dropping is completed within 3 - 4 h, and then keep the temperature at 15°C for heat preservation reaction for 2 h. After the reaction is completed, remove the solvent by reduced pressure to obtain intermediate A;

[0061] S2. Take 200 g (0.41 mol) of the above-obtained intermediate A, put it into the reactor, and then add 600 mL of 200# solvent oil and 31.13 g (0.43 mol) of tert-butylamine to it. Control the reaction temperature at 175°C and the reaction time at 3.5 h. Stop the reaction and cool down to 0°C, and the product will precipitate, and then filter to obtain intermediate B;

[0062] S3. Take 200 g (0.37 mol) of the above-obtained intermediate B, put it into the reactor, and then add 282.20 g (1.64 mol) of 2-ethylhexyl acetate, 600 mL of xylene and 1.95 g (0.028 mol) of potassium methoxide to it. After adding the materials, raise the temperature to 125°C, and continue the reaction at this temperature for 5.5 h. After the reaction is completed, cool to room temperature, wash with water and then separate the lower aqueous solution by liquid separation. Remove the excess organic solvent by rotary evaporation to obtain the crude product of the target product HEB, and then recrystallize it with a mixed solution of ethanol and water (10:1) to obtain high-purity HEB.

[0063] After calculation, the total yield of the three-step reaction is greater than 89%. The chemical structure of the obtained final product HEB was confirmed by nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum analysis, and its purity was detected by liquid chromatography to be 98.45%.

[0064] Example 5

[0065] This example provides a preparation method of the ultraviolet absorber HEB, and the specific steps include:

[0066] S1. Charge 138.3 g (0.75 mol) of cyanuric chloride, 75.6 g (0.90 mol) of sodium bicarbonate and 300 mL of acetonitrile into the reactor. Control the reaction temperature at 20 °C, stir to dissolve, and slowly add dropwise a 500 mL acetonitrile solution containing 323.99 g (2.36 mol) of p-aminobenzoic acid at this temperature. Finish the addition dropwise within 3 - 4 h, then keep the reaction at 20 °C for 2 h. After the reaction is completed, remove the solvent under reduced pressure to obtain intermediate A;

[0067] S2. Take 200 g (0.41 mol) of the above-obtained intermediate A, charge it into the reactor, and then add 600 mL of 200# solvent oil and 33.20 g (0.45 mol) of tert-butylamine thereto. Control the reaction temperature at 180 °C and the reaction time at 3 h. Stop the reaction and cool it to 0 °C, and the product will precipitate, then filter to obtain intermediate B;

[0068] S3. Take 200 g (0.37 mol) of the above-obtained intermediate B, charge it into the reactor, and then add 255.27 g (1.48 mol) of 2-ethylhexyl acetate, 600 mL of toluene and 1.95 g (0.028 mol) of potassium methoxide thereto. After the addition is completed, raise the temperature to 110 °C and continue the reaction at this temperature for 5 h. After the reaction is completed, cool it to room temperature, wash it with water and then separate the lower aqueous solution by liquid separation. Remove the excess organic solvent by rotary evaporation to obtain the crude product of the target product HEB, and then recrystallize it with a mixed solution of ethanol and water (10:2) to obtain high-purity HEB.

[0069] After calculation, the total yield of the three-step reaction is greater than 89%. The chemical structure of the obtained final product HEB is confirmed by nuclear magnetic resonance hydrogen spectrum and nuclear magnetic resonance carbon spectrum analysis. Its purity is detected by liquid chromatography to be 98.55%.

[0070] The above is only the preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and should be covered by the protection scope of the present invention.

Claims

1. A method for preparing ultraviolet absorber HEB, characterized in that the steps include: S1. Add a second solution containing p-aminobenzoic acid to a first solution containing cyanuric chloride and an alkaline agent at 0-20° C., so that p-aminobenzoic acid replaces three chlorine atoms on cyanuric chloride, and separates and obtains intermediate A; S2, adding the intermediate A and tert-butylamine into 200# solvent oil, reacting the intermediate A and tert-butylamine at 160-180° C. for 3-5 hours, and after the reaction, performing solid-liquid separation and collecting the solid to obtain intermediate B; S3, adding the intermediate B, 2-ethylhexyl acetate and an alkaline agent into an organic solvent, reacting at 110-130° C. for 5-7 hours, cooling to room temperature after the reaction, collecting the organic phase after washing with water, removing the organic solvent, and recrystallizing to obtain the ultraviolet absorber HEB.

2. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S1, the molar ratios of cyanuric chloride, p-aminobenzoic acid and alkaline reagent are 1:3.1-3.3:1.1-1.3 respectively.

3. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S1, the solvents in the first solution and the second solution are the same, both of which are acetonitrile or acetone.

4. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S2, the molar ratio of the intermediate A to tert-butylamine is 1:1.04-1.

1.

5. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S2, the solvent is 200# solvent oil.

6. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S3, the molar ratios of the intermediate B, 2-ethylhexyl acetate and the alkaline reagent are 1:3.5-5:0.05-0.1 respectively.

7. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S3, the organic solvent is toluene or xylene.

8. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: The alkaline agent is selected from any one of sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and potassium methoxide.

9. The method for preparing the ultraviolet absorber HEB according to claim 1, characterized in that: In step S3, the obtained solid is recrystallized using a mixture of ethanol and water.

10. Ultraviolet absorber HEB, characterized in that The ultraviolet absorber HEB is prepared according to the preparation method according to any one of claims 1 to 9.

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