Synthesis method of 2, 2 '-dihydroxy-4, 4'-dimethoxybenzophenone

Abstract

The invention discloses a synthesis method of 2, 2 '-dihydroxy-4, 4'-dimethoxybenzophenone, which comprises the following steps: by taking 4-methoxysalicylic acid and 3-methoxyphenol as initial raw materials, carrying out esterification and Fries rearrangement reaction in the presence of a chlorination reagent and lewis acid to obtain the 2, 2 '-dihydroxy-4, 4'-dimethoxybenzophenone; post-treatment is carried out after the esterification and Fries rearrangement reaction, wherein the reaction liquid is added into water, and stirring is carried out to separate out a crude product; dissolving the crude product at high temperature by using an alcohol solvent; then adding activated carbon for high-temperature decoloration; and finally filtering and cooling filtrate to separate out a finished product. The synthesis method has the advantages that the safety of the raw materials is higher, particularly, the generation of impurities such as monohydroxy (monomethoxy), trihydroxy (trimethoxy), tetrahydroxy (tetramethoxy) and dihydroxy (dimethoxy) isomeride can be avoided, the post-treatment is simple, the product purity and the reaction yield are higher, and the synthesis method is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone. Background Art

[0002] 2,2'-Dihydroxy-4,4'-dimethoxybenzophenone, also known as UV absorber BP-6, yellow powder solid, molecular formula: C 15 H 14 O5, relative weight: 274.27, CAS number: 131-54-4.

[0003] 2,2'-Dihydroxy-4,4'-dimethoxybenzophenone is a water-soluble benzophenone-type UV absorber with the characteristics of high absorption efficiency, non-toxicity, no teratogenic side effects, good light and thermal stability, etc. It is the most commonly used light stabilizer at present. It is a kind of substance that can strongly and selectively absorb high-energy ultraviolet light, convert energy, and release or consume energy in the form of heat energy or harmless low-energy radiation. It is mainly used in water-soluble chemical sunscreens, sunscreens, and lotions. It can also improve the color durability of dyed textiles, prevent wool textiles from yellowing, and prevent synthetic fiber fabrics from fading. At the same time, it can be used in hair products such as hair spray and mousse to prevent hair damage and whitening caused by ultraviolet radiation. It is widely used.

[0004] At present, there are two methods for the synthesis of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone: (A) 2,2',4,4'-tetramethoxybenzophenone removes two molecules of methyl to obtain 2,2'-dihydroxy-4,4'-dimethoxybenzophenone; the reaction formula is as follows: .

[0005] (B), 2,2',4,4'-tetrahydroxybenzophenone is methylated with dimethyl sulfate to obtain 2,2'-dihydroxy-4,4'-dimethoxybenzophenone; the reaction formula is as follows: .

[0006] However, regardless of method A or method B, the generation of monohydroxy (monomethoxy), trihydroxy (trimethoxy), tetrahydroxy (tetramethoxy) and dihydroxy (dimethoxy) isomer impurities is unavoidable. These impurities are difficult to separate and purify, resulting in low product purity / reaction yield, and are not suitable for large-scale industrial production. In addition, the raw material dimethyl sulfate used in method B is a highly toxic substance and has low safety. Summary of the invention

[0007] The object of the present invention is to solve the above problems and provide a method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone which has high safety, high reaction yield and high product purity.

[0008] The technical solution for achieving the purpose of the present invention is: a method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, characterized in that: 4-methoxysalicylic acid and 3-methoxyphenol are used as starting materials, and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone is obtained by esterification+Fries rearrangement reaction in the presence of a chlorination agent and a Lewis acid.

[0009] The reaction formula is as follows: .

[0010] The molar ratio of the 4-methoxysalicylic acid to the 3-methoxyphenol is 1:1 to 1:1.5.

[0011] The chlorination agent is phosphorus oxychloride, thionyl chloride or phosphorus pentachloride; the molar ratio of the 4-methoxysalicylic acid to the chlorination agent is 1:1.5 to 1:2.5.

[0012] The Lewis acid is zinc chloride or ferric chloride; the molar ratio of the 4-methoxysalicylic acid to the Lewis acid is 1:1 to 1:1.5.

[0013] The esterification+Fries rearrangement reaction is carried out in the presence of an organic solvent; the organic solvent is sulfolane; and the weight ratio of the 4-methoxysalicylic acid to the sulfolane is 1:2 to 1:5.

[0014] The esterification + Fries rearrangement reaction temperature is 45-75° C., and the reaction time is 4-7 hours.

[0015] The esterification + Fries rearrangement reaction also includes post-treatment, which is as follows: adding the reaction solution into water and stirring to precipitate a crude product; then dissolving the crude product with an alcohol solvent at high temperature; then adding activated carbon for high-temperature decolorization; and finally filtering and cooling the filtrate to precipitate the finished product.

[0016] The temperature of the water is 0-20°C, preferably 0-5°C.

[0017] The amount of water used is 8 to 20 times the weight of the 4-methoxysalicylic acid.

[0018] The alcohol solvent is ethanol or isopropanol.

[0019] The amount of the alcohol solvent used is 5 to 12 times the weight of the 4-methoxysalicylic acid.

[0020] The amount of the activated carbon used is 8-20% of the weight of the 4-methoxysalicylic acid.

[0021] The present invention has positive effects: the synthetic method of the present invention has high raw material safety, especially can avoid the generation of impurities such as monohydroxy (monomethoxy), trihydroxy (trimethoxy), tetrahydroxy (tetramethoxy) and dihydroxy (dimethoxy) isomers, and the post-treatment is simple, the product purity and reaction yield are high, and it is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The DSC spectrum of the target product obtained in Example 1 is shown in FIG.

[0023] Figure 2 The LC-MS spectrum of the target product obtained in Example 1 is shown in FIG. DETAILED DESCRIPTION

[0024] (Example 1) The synthesis method of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone in this embodiment is as follows: ① Add 50.0g of 4-methoxysalicylic acid (0.30mol), 45.0g of 3-methoxyphenol (0.36mol) and 150g of cyclopentane sulfone into a 500mL three-necked flask, stir to dissolve, then add 92.0g of phosphorus oxychloride (0.60mol) and 45.0g of zinc chloride (0.33mol), raise the temperature to 55-60℃, and stir to react for 5h.

[0025] ② Add 500g of water to a 1000mL three-necked flask, cool to 0-5°C, slowly drop the reaction solution obtained in step ①, control the temperature below 20°C during the dropwise addition, and stir for 2h after the dropwise addition. Filter, rinse the filter cake with a small amount of water, and then add it to the above 1000mL three-necked flask, then add 315g of ethanol, heat to 75-78°C, stir to dissolve, then add 8g of activated carbon, and stir at 75-78°C for 3 hours. 0min, filter, slowly cool the filtrate to 10-15°C, add 100g of water dropwise, continue stirring at 10-15°C for 1h, filter, rinse the filter cake with a small amount of water, place it in a 70-80°C oven and dry it under reduced pressure for 15h to obtain 68.1g of yellow 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, with a yield of 83.5%, HPLC purity of 99.7%, and a melting point of 141.46°C (see Figure 1 ).

[0026] The ESI-MS spectrum of the target product is shown in Figure 2 ,Depend on Figure 2It can be seen that its molecular weight is 274.0 (M+H), which is basically consistent with 2,2'-dihydroxy-4,4'-dimethoxybenzophenone.

[0027] (Example 2) The synthesis method of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone in this embodiment is as follows: ① Add 50.0g of 4-methoxysalicylic acid (0.30mol), 47.0g of 3-methoxyphenol (0.38mol) and 150g of cyclopentane into a 500mL three-necked flask, stir to dissolve, then add 75.0g of thionyl chloride (0.63mol) and 46.0g of zinc chloride (0.34mol), raise the temperature to 60-65℃, and stir to react for 5h.

[0028] ② Add 500g of water to a 1000mL three-necked flask, cool to 0-5°C, slowly drop the reaction solution obtained in step ①, control the temperature below 20°C during the dropwise addition, rinse the reaction flask with a small amount of water after the dropwise addition, control the temperature below 20°C and stir for 2h, filter, rinse the filter cake with a small amount of water, still add it to the above 1000mL three-necked flask, then add 393g of isopropanol, heat to 77-82°C, stir to dissolve, then add 5g of activated carbon, stir at 77-82°C for 30min, filter, slowly cool the filtrate to 10-15°C, continue stirring for 1h, filter, rinse the filter cake with a small amount of isopropanol, place it in a 60-70°C oven and dry it under reduced pressure for 8h to obtain 62.9g of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, with a yield of 77.1%, yellow appearance, HPLC purity of 99.6%, and a melting point of 141.38°C.

[0029] (Example 3) The synthesis method of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone in this embodiment is as follows: ① Add 50.0g of 4-methoxysalicylic acid (0.30mol), 45.0g of 3-methoxyphenol (0.36mol) and 200g of cyclopentane sulfone into a 500mL three-necked flask, stir to dissolve, then add 105.0g of phosphorus pentachloride (0.50mol) and 57.0g of ferric chloride (0.35mol), raise the temperature to 50-55℃, and stir to react for 5h.

[0030] ② Add 700g of water to a 2000mL three-necked flask, cool to 0-5°C, slowly drop the reaction solution obtained in step ①, control the temperature below 20°C during the dropwise addition, rinse the reaction flask with a small amount of water after the dropwise addition, control the temperature below 20°C and stir for 2h, filter, rinse the filter cake with a small amount of water, still add it to the above 2000mL three-necked flask, then add 393g of isopropanol, heat to 77-82°C, stir to dissolve, then add 5g of activated carbon, stir at 77-82°C for 30min, filter, slowly cool the filtrate to 10-15°C, continue stirring for 1h, filter, rinse the filter cake with a small amount of isopropanol, place it in a 60-70°C oven and dry it under reduced pressure for 8h to obtain 69.3g of 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, with a yield of 85.0%, yellow appearance, HPLC purity of 99.8%, and a melting point of 141.48°C.

Claims

1. A method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, characterized in that: 4-methoxysalicylic acid and 3-methoxyphenol were used as starting materials, and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone was obtained by esterification and Fries rearrangement in the presence of a chlorination agent and a Lewis acid.

2. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 1, characterized in that: The molar ratio of the 4-methoxysalicylic acid to the 3-methoxyphenol is 1:1 to 1:1.

5.

3. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 1, characterized in that: The chlorination agent is phosphorus oxychloride, thionyl chloride or phosphorus pentachloride; the molar ratio of the 4-methoxysalicylic acid to the chlorination agent is 1:1.5 to 1:2.

5.

4. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 1, characterized in that: The Lewis acid is zinc chloride or ferric chloride; the molar ratio of the 4-methoxysalicylic acid to the Lewis acid is 1:1 to 1:1.

5.

5. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 1, characterized in that: The esterification+Fries rearrangement reaction is carried out in the presence of an organic solvent; the organic solvent is sulfolane; and the weight ratio of the 4-methoxysalicylic acid to the sulfolane is 1:2 to 1:

5.

6. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 1, characterized in that: The esterification + Fries rearrangement reaction temperature is 45-75° C., and the reaction time is 4-7 hours.

7. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 1, characterized in that: The esterification + Fries rearrangement reaction also includes post-treatment, which is as follows: adding the reaction solution into water and stirring to precipitate a crude product; then dissolving the crude product with an alcohol solvent at high temperature; then adding activated carbon for high-temperature decolorization; and finally filtering and cooling the filtrate to precipitate the finished product.

8. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 7, characterized in that: The temperature of the water is 0-20° C.; the amount of the water is 8-20 times the weight of the 4-methoxysalicylic acid.

9. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 7, characterized in that: The alcohol solvent is ethanol or isopropanol; the amount of the alcohol solvent used is 5 to 12 times the weight of the 4-methoxysalicylic acid.

10. The method for synthesizing 2,2'-dihydroxy-4,4'-dimethoxybenzophenone according to claim 7, characterized in that: The amount of the activated carbon used is 8-20% of the weight of the 4-methoxysalicylic acid.

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