Preparation method of avobenzone

Abstract

The invention relates to a preparation method of avobenzone, which comprises the steps of preparation of an intermediate 1, preparation of an avobenzone crude product, refining of avobenzone and the like, the molar yield of avobenzone prepared by the method is more than 92%, and the content of avobenzone reaches 98.5-99.8%.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical synthesis, and relates to a preparation method of avobenzone. BACKGROUND

[0002] Avobenzone is an oil-soluble organic compound, and has the property of absorbing UVA waves of 320-400 nm. The substance was approved by the US Food and Drug Administration in 1988 for use as a sunscreen, and is widely used in sunscreens, lipsticks and other cosmetics.

[0003] Regarding the preparation method of avobenzone, the prior art discloses the following: Chinese patent CN109867597A discloses that avobenzone is prepared by Claisen condensation using p-tert-butyl acetophenone and methyl p-methoxybenzoate as raw materials and sodium amide as a strong alkaline catalyst. However, sodium amide is easily converted into sodium azide (NaN3), which has an explosion risk, and there is a great safety risk in the production process, which is not suitable for industrial production.

[0004] Chinese patent CN113754521A discloses that p-methoxyacetophenone and methyl p-tert-butyl benzoate are reacted at 90-110℃ for 4-6h using xylene as a solvent and sodium methoxide as a catalyst to obtain avobenzone.

[0005] Therefore, it is still necessary to study the preparation of avobenzone, and to develop a preparation method with mild reaction conditions, without toluene or xylene solvent, and stable quality and safety. SUMMARY

[0006] The purpose of the present application is to solve the defects in the prior art and provide a preparation method of avobenzone.

[0007] The purpose of the present application is achieved by the following scheme: a preparation method of avobenzone, comprising the following steps: Step S1: preparation of intermediate 1; (1) water, p-tert-butyl benzaldehyde are added to a reaction container, and stirring is performed to reduce the temperature to 5-10℃; dimethyl phosphite is added, and phosphoric acid, ZSM-5 type molecular sieve catalyst, and the reaction temperature is controlled at 25-30℃, and stirring is performed for 3-5h; after the reaction is completed, ethyl acetate, p-methoxyacetophenone, and diisopropylethylamine are added; the reaction temperature is controlled at 15-30℃, and the reaction is performed for 3-5h.

[0008] (2) filtration, static separation, and taking the organic phase (intermediate 1) for standby.

[0009] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add a catalyst, slowly drop the peracetic acid solution, control the temperature at 30 ~ 35℃, and stir for 3 ~ 4h; wherein the catalyst is 3% ~ 7% Pd / C.

[0010] (2) Let it stand and separate the phases, take the organic phase, and distill under reduced pressure to obtain crude avobenzone.

[0011] Step S3: Refining of avobenzone (1) Dissolve the crude avobenzone prepared in step S2 in petroleum ether; (2) Add saturated brine, stir for 30 minutes or more, add sodium hydroxide solution, adjust the pH value to 8.0 ~ 8.5, control the temperature at 30 ~ 35℃, and stir for 2 ~ 3h; let it stand and separate the layers, discard the aqueous phase, and obtain the oil phase; (3) Optionally, repeat step 1 ~ 2 times in step (2) of step S3; (4) Add the oil phase in step (2) or (3) to a rectification column, control the pressure at 5 ~ 8mmHg, collect the fraction at 230 ~ 250℃, condense to obtain avobenzone liquid, cool to 45 ~ 50℃, and melt crystallize to obtain avobenzone crystals.

[0012] In some embodiments of the present application, in step S1, the molar ratio of p-t-butylbenzaldehyde to dimethyl phosphite is 1:1 ~ 3, preferably 1:1.3 ~ 1.5.

[0013] In some embodiments of the present application, in step S1, the weight ratio of p-t-butylbenzaldehyde to ZSM-5 type molecular sieve catalyst is 1:0.1 ~ 0.2, preferably 1:0.1 ~ 0.15.

[0014] In some embodiments of the present application, in step S1, the molar ratio of p-t-butylbenzaldehyde to p-methoxyacetophenone is 1:1 ~ 3, preferably 1:1.1 ~ 1.3.

[0015] In some embodiments of the present application, in step S1, the molar ratio of p-t-butylbenzaldehyde to diisopropylethylamine is 1:1 ~ 5; preferably 1:3 ~ 4.

[0016] In some embodiments of the present application, in step S2, the catalyst is 3% ~ 7% Pd / C; preferably 5% Pd / C.

[0017] In some embodiments of the present application, in step S2, the molar ratio of p-t-butylbenzaldehyde to peracetic acid is 1:1.5 ~ 1.7.

[0018] In some embodiments of the present application, in step S2, the peracetic acid is a 15% to 18% peracetic acid aqueous solution.

[0019] In some embodiments of the present application, in step S2, the dropping time of peracetic acid is not less than 2 hours, preferably 3 to 4 hours.

[0020] In some embodiments of the present application, in step S2, the molar ratio of tert-butylbenzaldehyde to peracetic acid is 1:1.5 to 2.

[0021] In some embodiments of the present application, in step S3, the weight to volume ratio of the crude avobenzone to petroleum ether is 1:2 to 5.

[0022] In some embodiments of the present application, in step S3, the weight to volume ratio of the crude avobenzone to saturated brine is 1:2 to 3.

[0023] In some embodiments of the present application, in step S3, the sodium hydroxide solution is a sodium hydroxide solution with a pH of 9.5 to 10.

[0024] The present application has the following beneficial effects: (1) The preparation method provided by the present application has mild reaction conditions and is suitable for industrial production. (2) The avobenzone prepared by the method of the present application has a molar yield of 92% or more and a content of 98.5% to 99.8%; (3) The avobenzone obtained by the present application has stable quality. DETAILED DESCRIPTION

[0025] The present application discloses a preparation method of avobenzone. Those skilled in the art can refer to the content of the present application, combine the relevant principles of chemical synthesis, and appropriately improve the process parameters to realize it. It is particularly pointed out that all similar substitutions and changes are obvious to those skilled in the art, and they are considered to be included in the scope of the present application. The application of the present application has been described by the preferred embodiments, and the relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present application to realize and apply the present application technology.

[0026] In order to better understand the present application without limiting the scope of the present application, all numbers and other numerical values used in this application to express amounts, percentages and other values should be understood as being modified by the word "about" in all cases. Each numerical parameter should be considered to be at least as accurate as the rounding methods used by the reporting method and obtained by conventional rounding methods.

[0027] The application is further illustrated by the following examples, but the examples do not limit the application in any way.

[0028] Example 1: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400 ml, p-tert-butyl benzaldehyde 162 g (1.0 mol) into a reaction vessel, and stir to cool to 5-10°C; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 20 g, and control the reaction temperature at 27-28°C; stir for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyphenylacetone 181.5 g (1.21 mol), and diisopropyl ethylamine 438.6 g (3.4 mol); control the reaction temperature at 20-25°C, and react for 4 h; (2) Filter, and separate the phases by standing; take the organic phase (intermediate 1) for standby.

[0029] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 16% peracetic acid (1.6 mol) solution; the drop time is 3 h, the temperature is controlled at 30-35°C, and the reaction is stirred for 3.4 h; (2) Separate the phases by standing, take the organic phase, and distill under reduced pressure to obtain crude avobenzone 279.3 g (0.95 mol) with a purity of 96.7%.

[0030] Example 2: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400 ml, p-tert-butyl benzaldehyde 162 g (1.0 mol) into a reaction vessel, and stir to cool to 5-10°C; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 20 g, and control the reaction temperature at 27-28°C; stir for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyphenylacetone 181.5 g (1.21 mol), and diisopropyl ethylamine 438.6 g (3.4 mol); control the reaction temperature at 20-25°C, and react for 4 h; (2) Filter, and separate the phases by standing; take the organic phase (intermediate 1) for standby.

[0031] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15g, drop 18% peracetic acid (1.7mol) solution, drop time is 2.5 hours, control temperature 30 ~ 35℃, stir reaction 3h.

[0032] (2) Stand for phase separation, take the organic phase, reduce pressure distillation, get crude avobenzone 270.5g (0.92mol); purity 96.4%.

[0033] Example 3: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400ml, p-tert-butyl benzaldehyde 162g (1.0mol) to the reaction container, stir and cool to 5~10℃; add dimethyl phosphite 160.6g (1.46mol), add 3mol / L phosphoric acid solution 20ml, ZSM-5 type molecular sieve catalyst 20g, control the reaction temperature at 25~27℃, stir for 3.2h, after the reaction is completed, add ethyl acetate 600ml, p-methoxyphenylacetone 192g (1.28mol), diisopropyl ethylamine 477.3g (3.7mol); control the reaction temperature at 18~22℃, react for 3.5h; (2) Filter, stand for phase separation, take the organic phase (intermediate 1), ready for use.

[0034] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15g, drop 15% peracetic acid (1.5mol) solution, drop time is 3.8 hours; control temperature 30 ~ 35℃, stir reaction 4h; (2) Stand for phase separation, take the organic phase, reduce pressure distillation, get crude avobenzone 270.4g (0.93mol), purity 96.1%.

[0035] Comparative Example 1: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400ml, p-tert-butyl benzaldehyde 162g (1.0mol) to the reaction container, stir and cool to 5~10℃; add dimethyl phosphite 154g (1.4mol), add 3mol / L hydrochloric acid solution 60ml, ZSM-5 type molecular sieve catalyst 20g, control the reaction temperature at 27~28℃, stir for 4h, after the reaction is completed, add ethyl acetate 500ml, p-methoxyphenylacetone 181.5g (1.21mol), diisopropyl ethylamine 438.6g (3.4mol); control the reaction temperature at 20~25℃, react for 4h; (2) Filter, stand and separate phases, and take the organic phase (intermediate 1) for standby.

[0036] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 16% peracetic acid (1.6 mol) solution, the drop time is 3 hours, control the temperature at 30 ~ 35℃, and stir for 3.4 h; (2) Stand and separate phases, take the organic phase, and reduce pressure distillation to obtain crude avobenzone 202.9 g (0.69 mol), purity 91.5%.

[0037] Comparative Example 2: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400 ml, p-tert-butylbenzaldehyde 162 g (1.0 mol) to the reaction container, and stir to cool to 5 ~ 10℃; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 20 g, control the reaction temperature at 27 ~ 28℃, and stir for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyacetophenone 181.5 g (1.21 mol), and triethylamine 343.4 g (3.4 mol); control the reaction temperature at 20 ~ 25℃, and react for 4 h; (2) Filter, stand and separate phases, and take the organic phase (intermediate 1) for standby.

[0038] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 16% peracetic acid (1.6 mol) solution, the drop time is 3 hours, control the temperature at 30 ~ 35℃, and stir for 3.4 h; (2) Stand and separate phases, take the organic phase, and reduce pressure distillation to obtain crude avobenzone 202.9 g (0.69 mol), purity 91.5%. Comparative Example 3: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Into a reaction vessel, add purified water 400 ml, p-tert-butylbenzaldehyde 162 g (1.0 mol), and stir to cool to 5-10°C; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 5 g, and control the reaction temperature at 27-28°C; stir to react for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyphenylacetophenone 181.5 g (1.21 mol), and diisopropylethylamine 438.6 g (3.4 mol); control the reaction temperature at 20-25°C, and react for 4 h; (2) Filter, separate the phases, and take the organic phase (intermediate 1) for standby use.

[0039] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 16% peracetic acid (1.6 mol) solution; the drop time is 3 h, the temperature is controlled at 30-35°C, and the stirring is reacted for 3.4 h. (2) Separate the phases, take the organic phase, and distill under reduced pressure to obtain crude avobenzone 141.2 g (0.48 mol) with a purity of 86.9%.

[0040] Comparative Example 4: Preparation of crude avobenzone Step S1: Preparation of intermediate 1 (1) Into a reaction vessel, add purified water 400 ml, p-tert-butylbenzaldehyde 162 g (1.0 mol), and stir to cool to 5-10°C; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 20 g, and control the reaction temperature at 27-28°C; stir to react for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyphenylacetophenone 181.5 g (1.21 mol), and diisopropylethylamine 438.6 g (3.4 mol); control the reaction temperature at 20-25°C, and react for 4 h; (2) Filter, separate the phases, and take the organic phase (intermediate 1) for standby use.

[0041] Step S2: Preparation of crude avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 16% peracetic acid (1.6 mol) solution; the drop time is 3 h, the temperature is controlled at 30-35°C, and the stirring is reacted for 3.4 h. (2) Separate the phases, take the organic phase, and distill under reduced pressure to obtain crude avobenzone 141.2 g (0.48 mol) with a purity of 86.9%.

[0042] Preparation of crude Avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400 ml, p-tert-butyl benzaldehyde 162 g (1.0 mol) into the reaction vessel, and stir to cool to 5-10 °C; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 20 g, and control the reaction temperature at 27-28 °C, and stir to react for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyphenylacetone 181.5 g (1.21 mol), and diisopropyl ethylamine 438.6 g (3.4 mol); control the reaction temperature at 20-25 °C, and react for 4 h; (2) Filter, and separate the phases by standing, and take the organic phase (intermediate 1) for standby.

[0043] Step S2: Preparation of crude Avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 25% peracetic acid (1.6 mol) solution, the drop time is 3 hours, the temperature is controlled at 30-35 °C, and stir to react for 3.4 h; (2) Separate the phases by standing, take the organic phase, and distill under reduced pressure to obtain crude Avobenzone 276.4 g (0.94 mol) with a purity of 92.7%.

[0044] Preparation of crude Avobenzone Step S1: Preparation of intermediate 1 (1) Add purified water 400 ml, p-tert-butyl benzaldehyde 162 g (1.0 mol) into the reaction vessel, and stir to cool to 5-10 °C; add dimethyl phosphite 154 g (1.4 mol), 3 mol / L phosphoric acid solution 20 ml, ZSM-5 type molecular sieve catalyst 20 g, and control the reaction temperature at 27-28 °C, and stir to react for 4 h; after the reaction is completed, add ethyl acetate 500 ml, p-methoxyphenylacetone 181.5 g (1.21 mol), and diisopropyl ethylamine 438.6 g (3.4 mol); control the reaction temperature at 20-25 °C, and react for 4 h; (2) Filter, and separate the phases by standing, and take the organic phase (intermediate 1) for standby.

[0045] Step S2: Preparation of crude Avobenzone (1) Take the organic phase (containing intermediate 1) of step S1, add 5% Pd / C 15 g, and drop 25% peracetic acid (1.6 mol) solution, the drop time is 3 hours, the temperature is controlled at 30-35 °C, and stir to react for 3.4 h; (2) The organic phase was obtained by standing and phase separation, and was distilled under reduced pressure to obtain 267.5 g (0.91 mol) of the product with a purity of 90.8%.

[0046] Example 4: Preparation of Avobenzone Step S3: Purification of Avobenzone (1) 500 g of the crude Avobenzone prepared according to the method of Example 1 was dissolved in 1200 ml of petroleum ether; (2) 1000 ml of saturated brine was added, and stirring was performed for 50 minutes. A sodium hydroxide solution with a pH of 9.8 was added dropwise to adjust the pH to 8.3, and the temperature was controlled at 30-35°C. Stirring was performed for 2.5 hours. The water phase was discarded after standing and phase separation to obtain an oil phase; (3) The oil phase of step (1) was added to a rectification tower, and the pressure was controlled at 5-8 mmHg. The fraction at 230-250°C was collected, and Avobenzone liquid was obtained by condensation. The temperature was lowered to 45-50°C, and Avobenzone crystals were obtained by melt crystallization. The yield was 96.3%, the content was 99.5%, and the total impurities were 0.5%.

[0047] Example 5: Preparation of Avobenzone Step S3: Purification of Avobenzone (1) 500 g of the crude Avobenzone prepared according to the method of Example 1 was dissolved in 1500 ml of petroleum ether; (2) 1500 ml of saturated brine was added, and stirring was performed for 60 minutes. A sodium hydroxide solution with a pH of 9.8 was added dropwise to adjust the pH to 8.3, and the temperature was controlled at 30-35°C. Stirring was performed for 2 hours. The water phase was discarded after standing and phase separation to obtain an oil phase; (3) Step 1 in step S3 was repeated once; (4) The oil phase in step (3) was added to a rectification tower, and the pressure was controlled at 5-8 mmHg. The fraction at 230-250°C was collected, and Avobenzone liquid was obtained by condensation. The temperature was lowered to 45-50°C, and Avobenzone crystals were obtained by melt crystallization. The yield was 96.0%, the content was 99.7%, and the total impurities were 0.3%.

[0048] Example 6: Preparation of Avobenzone Step S3: Purification of Avobenzone (1) 500 g of the crude Avobenzone prepared according to the method of Example 1 was dissolved in 2000 ml of petroleum ether; (2) 1200 ml of saturated brine was added, and stirring was performed for 45 minutes. A sodium hydroxide solution with a pH of 10 was added dropwise to adjust the pH to 8.5, and the temperature was controlled at 30-35°C. Stirring was performed for 3 hours. The water phase was discarded after standing and phase separation to obtain an oil phase; (3) Step 1 in step S3 was repeated twice; (4) The oil phase in step (2) is added into a rectifying column, the pressure is controlled at 5-8 mmHg, the fraction of 230-250°C is collected, and the liquid of avobenzone is condensed. The temperature is lowered to 45-50°C, and the crystal of avobenzone is obtained by melt crystallization. The yield is 95.6%, the content is 99.8%, and the total impurities are 0.2%.

[0049] Example 7: Preparation of avobenzone Step S3: Refining of avobenzone (1) 500 g of the crude avobenzone prepared according to the method of Example 2 is dissolved in 1500 ml of petroleum ether; (2) 1500 ml of saturated brine is added, stirred for 60 minutes, and a sodium hydroxide solution with pH of 9.8 is added dropwise to adjust the pH value to 8.3, and the temperature is controlled at 30-35°C, and stirred for 2 h. After standing and layering, the water phase is discarded, and the oil phase is obtained; (3) Step 1 in step S3 is repeated once; (4) The oil phase in step (3) is added into a rectifying column, the pressure is controlled at 5-8 mmHg, the fraction of 230-250°C is collected, and the liquid of avobenzone is condensed. The temperature is lowered to 45-50°C, and the crystal of avobenzone is obtained by melt crystallization. The yield is 95.6%, the content is 99.8%, and the total impurities are 0.2%.

[0050] Example 8: Preparation of avobenzone Step S3: Refining of avobenzone (1) 500 g of the crude avobenzone prepared according to the method of Example 3 is dissolved in 1500 ml of petroleum ether; (2) 1500 ml of saturated brine is added, stirred for 60 minutes, and a sodium hydroxide solution with pH of 9.8 is added dropwise to adjust the pH value to 8.3, and the temperature is controlled at 30-35°C, and stirred for 2 h. After standing and layering, the water phase is discarded, and the oil phase is obtained; (3) Step 1 in step S3 is repeated once; (4) The oil phase in step (3) is added into a rectifying column, the pressure is controlled at 5-8 mmHg, the fraction of 230-250°C is collected, and the liquid of avobenzone is condensed. The temperature is lowered to 45-50°C, and the crystal of avobenzone is obtained by melt crystallization. The yield is 95.6%, the content is 99.8%, and the total impurities are 0.2%.

[0051] Comparative Example 7: Preparation of avobenzone Step S3: Refining of avobenzone (1) 500 g of the crude avobenzone prepared according to the method of Example 1 is dissolved in 1500 ml of ethyl acetate; (2) Add saturated brine 1500 ml, stir for 60 minutes, drop in sodium hydroxide solution with pH value of 9.8, adjust pH value to 8.3, control temperature at 30 ~ 35℃, stir for 2 hours; stand for stratification, discard water phase, and obtain oil phase; (3) Repeat step 1 in (1) for one time in step S3; (4) Add oil phase in step (3) into rectifying column, control pressure at 5 ~ 8 mmHg, collect 230 ~ 250℃ fraction, condense to obtain avobenzone liquid, cool to 45 ~ 50℃, melt crystallization, and obtain avobenzone crystal; yield 96.8%, content 95.7%.

[0052] Preparation of avobenzone in Example 1 Step S3: Refining of avobenzone (1) Dissolve 500 g of crude avobenzone prepared according to the method in Example 1 into petroleum ether 1500 ml, (2) Add saturated brine 1500 ml, stir for 60 minutes, drop in sodium hydroxide solution with pH value of 9.8, adjust pH value to 11, control temperature at 30 ~ 35℃, stir for 2 hours; stand for stratification, discard water phase, and obtain oil phase; (3) Repeat step 1 in (1) for one time in step S3; (4) Add oil phase in step (3) into rectifying column, control pressure at 5 ~ 8 mmHg, collect 230 ~ 250℃ fraction, condense to obtain avobenzone liquid, cool to 45 ~ 50℃, melt crystallization, and obtain avobenzone crystal; yield 96.8%, content 95.7%.

[0053] Preparation of avobenzone in Example 1 Step S3: Refining of avobenzone (1) Dissolve 500 g of crude avobenzone prepared according to the method in Example 1 into petroleum ether 1500 ml, (2) Add saturated brine 1500 ml, stir for 60 minutes, drop in sodium hydroxide solution with pH value of 9.8, adjust pH value to 9, control temperature at 30 ~ 35℃, stir for 2 hours; stand for stratification, discard water phase, and obtain oil phase; (3) Repeat step 1 in (1) for one time in step S3; (4) Add oil phase in step (3) into rectifying column, control pressure at 5 ~ 8 mmHg, collect 230 ~ 250℃ fraction, condense to obtain avobenzone liquid, cool to 45 ~ 50℃, melt crystallization, and obtain avobenzone crystal; yield 96.3%, content 99.7%, total impurity 0.3%.

[0054] Preparation of Avobenzone Step S3: Refining of Avobenzone (1) 500 g of crude Avobenzone prepared according to the method of Example 1 was dissolved in 1500 ml of petroleum ether, (2) 1500 ml of saturated brine was added, and stirred for 60 minutes, and the temperature was controlled at 30 ~ 35°C, and stirred for 2 h; it was allowed to stand and separate into layers, and the water phase was discarded to obtain an oil phase; (3) Step (1) was repeated once; (4) The oil phase in step (3) was added to a rectifying column, the pressure was controlled at 5 ~ 8 mmHg, and the fraction at 230 ~ 250°C was collected, and Avobenzone liquid was obtained by condensation, and the temperature was lowered to 45 ~ 50°C, and Avobenzone crystals were obtained by melt crystallization; the yield was 96.5%, the content was 98.8%, and the total impurities were 1.2%.

[0055] Preparation of Avobenzone Step S3: Refining of Avobenzone (1) 500 g of crude Avobenzone prepared according to the method of Example 1 was dissolved in 1500 ml of petroleum ether, (2) 1500 ml of saturated brine was added, and stirred for 60 minutes, and the temperature was controlled at 30 ~ 35°C, and stirred for 2 h; it was allowed to stand and separate into layers, and the water phase was discarded to obtain an oil phase; (3) Step (1) was repeated once; (4) The oil phase in step (3) was added to a rectifying column, the pressure was controlled at 5 ~ 8 mmHg, and the fraction at 230 ~ 250°C was collected, and Avobenzone liquid was obtained by condensation, and the temperature was lowered to 45 ~ 50°C, and Avobenzone crystals were obtained by melt crystallization; the yield was 96.5%, the content was 98.8%, and the total impurities were 1.2%.

[0056] Preparation of Avobenzone Step S3: Refining of Avobenzone (1) 500 g of crude Avobenzone prepared according to the method of Example 1 was dissolved in 1500 ml of petroleum ether, (2) 1500 ml of saturated brine was added, and stirred for 60 minutes, and the temperature was controlled at 30 ~ 35°C, and stirred for 2 h; it was allowed to stand and separate into layers, and the water phase was discarded to obtain an oil phase; (3) Step (1) was repeated once; (4) The oil phase in step (3) is added into a rectifying column, the pressure is controlled at 5-8 mmHg, the fraction of 230-250℃ is collected, and the avenanthorl liquid is condensed to obtain avenanthorl crystals by melt crystallization at 45-50℃; the yield is 95.9%, the content is 96.4%, and the total impurities are 3.6%.

[0057] Preparation of avenanthorl Step S3: Refining of avenanthorl (1) 500 g of avenanthorl crude product prepared according to the method of Comparative Example 6 is dissolved in 1500 ml of petroleum ether, (2) The solution is added into 1500 ml of saturated brine, stirred for 60 minutes, and a sodium hydroxide solution with pH of 9.8 is added dropwise to adjust the pH value to 8.3, and the temperature is controlled at ℃, and stirred for 2 h; after standing and layering, the water phase is discarded to obtain an oil phase; (3) Step 1 in step S3 is repeated once; (4) The oil phase in step (3) is added into a rectifying column, the pressure is controlled at 5-8 mmHg, the fraction of 230-250℃ is collected, and the avenanthorl liquid is condensed to obtain avenanthorl crystals by melt crystallization at 45-50℃; the yield is 95.3%, the content is 95.1%, and the total impurities are 4.9%.

[0058] Example 9: Stability test results 25℃±2℃ / 40%±5% RH, placed for 1 month, and the content and impurities are detected, as follows.

[0059] The avenanthorl prepared by the method has high content (or purity) and stable quality.

[0060] Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Although the present application is described in detail with reference to the foregoing embodiments, those skilled in the art can modify the technical solutions recorded in the foregoing embodiments, or make equivalent replacements to some technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing avobenzone, comprising the following steps: Step S1: Preparation of intermediate 1; (1) Add water and p-tert-butylbenzaldehyde to the reaction vessel, stir and cool to 5-10℃; add dimethyl phosphite and phosphoric acid, ZSM-5 molecular sieve catalyst, control the reaction temperature at 25-30℃, stir and react for 3-5h; after the reaction is completed, add ethyl acetate, p-methoxyacetophenone, and diisopropylethylamine; control the reaction temperature at 15-30℃ and react for 3-5h. (2) Filter, let stand and separate phases, take the organic phase (intermediate 1) for later use; Step S2: Preparation of crude avobenzone (1) Take the organic phase from step S1 (including intermediate 1), add the catalyst, slowly add peracetic acid solution, control the temperature at 30-35℃, and stir the reaction for 3-4 hours; wherein, The catalyst is 3% to 7% Pd / C; (2) Allow the phases to separate by standing, take the organic phase, and distill under reduced pressure to obtain crude avobenzone; Step S3: Refining Avobenzone (1) Dissolve the crude avobenzone prepared in step S2 in petroleum ether. (2) Add to saturated saline solution, stir for more than 30 minutes, add sodium hydroxide solution, adjust the pH value to 8.0~8.5, control the temperature at 30~35℃, stir for 2~3 hours; let stand to separate into layers, discard the aqueous phase, and obtain the oil phase; (3) Optionally, repeat step 1 to 2 of step (2) in step S3; (4) Add the oil phase from step (2) or (3) into the distillation column, control the pressure to 5-8 mmHg, collect the fraction at 230-250℃, condense to obtain avobenzone liquid, cool to 45-50℃, melt and crystallize to obtain avobenzone crystals.

2. The preparation method according to claim 1, characterized in that, In step S1, the molar ratio of p-tert-butylbenzaldehyde to dimethyl phosphite is 1:1~3, preferably 1:1.3~1.

5.

3. The preparation method according to claim 1, characterized in that, In step S1, the weight ratio of p-tert-butylbenzaldehyde to ZSM-5 molecular sieve catalyst is 1:0.1~0.2, preferably 1:0.1~0.

15.

4. The preparation method according to claim 1, characterized in that, In step S1, the molar ratio of p-tert-butylbenzaldehyde to p-methoxyacetophenone is 1:1 to 3, preferably 1:1.1 to 1.

3.

5. The preparation method according to claim 1, characterized in that, In step S1, the molar ratio of p-tert-butylbenzaldehyde to diisopropylethylamine is 1:1~5; preferably 1:3~4.

6. The preparation method according to claim 1, characterized in that, In step S2, the catalyst is 5% Pd / C.

7. The preparation method according to claim 1, characterized in that, In step S2, the molar ratio of p-tert-butylbenzaldehyde to peracetic acid is 1:1.5 ~ 1.

7.

8. The preparation method according to claim 1, characterized in that, In step S2, the peracetic acid is a 15% to 18% aqueous solution of peracetic acid.

9. The preparation method according to claim 1, characterized in that, In step S2, the molar ratio of p-tert-butylbenzaldehyde to peracetic acid is 1:1.5~2.

10. The preparation method according to claim 1, characterized in that, In step S3, the sodium hydroxide solution is a sodium hydroxide solution with a pH of 9.5 to 10.

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