Synthesis process of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate

Abstract

The present invention provides a synthesis process of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate. In the present invention, a solid acid is used as a catalyst, 3-N,N-diethylaminophenol and phthalic anhydride are put into an organic solvent and refluxed; the organic solvent is recovered; then n-hexanol is added to the reaction solution to react to form hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate; then the catalyst is recovered by hot filtration, the organic solvent in the filtrate is recovered under reduced pressure, cooled and crystallized, and filtered to obtain a primary refined product; the mother liquor of the primary refinement is recovered and treated to recover 2-hydroxy-4-diethylamino-2'-carboxybenzophenone and n-hexanol respectively; the n-hexanol in the primary refined product is recovered under reduced pressure, and then secondary refinement is carried out using ethanol as a solvent, decolorized, filtered, cooled and crystallized, centrifuged, and dried to obtain hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate. By adopting the synthesis process of the present invention, the yield is effectively improved, and the production cost is reduced, which is suitable for large-scale production.

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemicals, and particularly to a synthesis process of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate. Technical Background

[0002] Hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate is an ultraviolet absorber added to cosmetics. This substance containing a benzophenone structure has strong absorption properties for ultraviolet light in the range of 320 - 400 nm. Currently, the main processes for synthesizing hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate mostly adopt a two-step synthesis method. In the first step, the intermediate 2-hydroxy-4-diethylamino-2'-carboxybenzophenone is prepared, and in the second step, an esterification reaction occurs under acidic catalysts such as sulfuric acid and methanesulfonic acid to obtain hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate. These acidic catalysts are used in large amounts, are prone to corrode the reaction kettle, and are usually directly discharged with the waste liquid, polluting the environment. Invisibly, it increases the production cost of the enterprise and fails to meet the requirements of green and high-quality production. In addition, the obtained hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate is mostly obtained by multiple recrystallizations to obtain the hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate product. Especially after the mother liquor of the first purification is distilled to recover the solvent, impurities and part of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate are enriched in the concentrate of the mother liquor of the first purification and are treated as solid waste. This preparation process has complex steps, low yield and is not suitable for large-scale production. Summary of the Invention

[0003] In view of this, the purpose of the present invention is to provide a new process for synthesizing hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate to solve the above problems.

[0004] The present invention synthesizes hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate by a two-step one-pot method. The catalyst used in this process is sulfuric acid supported on silica gel (H 2 SO 4 -SiO 4) The catalyst is a recyclable solid acid catalyst. This process refines and recovers the mother liquor of the primary refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate, and simultaneously hydrolyzes and reduces the hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate generated in the concentrated recovery of the primary refined mother liquor with alkali to 2-hydroxy-4-diethylamino-2'-carboxybenzophenone, and recovers them separately with n-hexanol. Finally, n-hexanol is recovered under reduced pressure from the primary refined product, the refining solvent is changed to ethanol, decolorized with activated carbon, filtered, cooled and crystallized, and centrifuged to obtain a product with qualified HPLC content and chromaticity. The hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate with low solvent residue is obtained by freeze-drying.

[0005] The technical solution adopted by the present invention to solve its technical problems is as follows:

[0006] A synthesis process of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate, comprising the following steps:

[0007] (1) Using a solid acid as a catalyst, 3-N,N-diethylaminophenol and phthalic anhydride are put into an organic solvent, and a Friedel-Crafts acylation reaction occurs to generate 2-hydroxy-4-diethylamino-2'-carboxybenzophenone;

[0008] (2) Subsequently, n-hexanol is added to the reaction solution in step (1), and an esterification reaction occurs with the 2-hydroxy-4-diethylamino-2'-carboxybenzophenone to generate hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate;

[0009] The reaction formula is as follows:

[0010]

[0011] (3) Subsequently, the catalyst is recovered by hot filtration and reused for the synthesis reaction. The organic solvent in the filtrate is recovered under reduced pressure, cooled and crystallized, and filtered to obtain a primary refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate. The primary refined mother liquor is recovered, and 2-hydroxy-4-diethylamino-2'-carboxybenzophenone and n-hexanol are recovered separately;

[0012] (4) n-hexanol is recovered under reduced pressure from the primary refined product, and then secondary refining is carried out with ethanol as the solvent (to facilitate the subsequent removal of solvent residue by drying), decolorized, filtered, cooled and crystallized, and centrifuged to obtain a product with qualified HPLC content and chromaticity, and freeze-dried to obtain the target hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate with low solvent residue.

[0013] Further, in step (1), the catalyst is a silica gel supported sulfuric acid catalyst; the organic solvent is at least one of toluene and xylene, and the material ratio of 3-N,N-diethylaminophenol to the organic solvent is 1:4 - 7 kg / L, preferably 1:4.5 - 5.5, and more preferably 1:5.

[0014] Further, the molar ratio of 3-N,N-diethylaminophenol, phthalic anhydride, the catalyst, and n-hexanol is 1:0.8 - 1.2:0.01 - 0.3:2 - 4, preferably 1:0.9 - 1.1:0.15 - 0.25:2.5 - 3.5, and more preferably 1:1:0.2:3.

[0015] Further, in step (2), the reaction time is 6 - 10 h.

[0016] Further, in step (3), the specific steps for the recovery treatment of the primary refined mother liquor are as follows: the primary refined mother liquor is concentrated under reduced pressure to obtain a concentrated product of the refined mother liquor; the concentrated product of the refined mother liquor is reacted with an alkali and water at 50 - 100 °C for 2 - 24 h, preferably at a reaction temperature of 80 - 100 °C and a reaction time of 6 - 8 h, then the system is separated by water, the lower aqueous phase is adjusted to pH 4 - 6 with sulfuric acid and filtered to obtain 2-hydroxy-4-diethylamino-2'-carboxybenzophenone, and the organic phase is distilled to recover the n-hexanol produced by hydrolysis.

[0017] Further, the alkali is at least one of sodium hydroxide, sodium carbonate, potassium hydroxide, or potassium carbonate.

[0018] Further, the weight of the alkali is 20% - 40% of the weight of the concentrated product of the refined mother liquor.

[0019] Further, in step (4), the decolorization is carried out by adding activated carbon for reflux decolorization, and the reflux time is 0.8 - 1.2 h. The mass ratio of the primary refined product, ethanol, and activated carbon is 1:1.5 - 2.5:0.11 - 0.12; the drying is freeze-drying.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] (1) The present invention synthesizes hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate by a two-step one-pot method. The synthesis process of the present invention can recycle the hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate in the concentrated product of the primary refined mother liquor, effectively improving the production efficiency, reducing the production cost, and being suitable for large-scale production.

[0022] (2) By using the synthesis process of the present invention, on the premise of improving the production efficiency, the usage amounts of acidic catalysts and organic solvents are effectively reduced, not only reducing the production cost but also being more environmentally friendly. Brief Description of the Drawings

[0023] Figure 1 This is the HPLC chart of the first refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate prepared in Example 1 of the present invention.

[0024] Figure 2 This is the HPLC chart of the concentrated refined mother liquor of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate prepared in Example 1 of the present invention.

[0025] Figure 3 This is the HPLC chart of 2-hydroxy-4-diethylamino-2'-carboxybenzophenone (intermediate) prepared in Example 1 of the present invention.

[0026] Figure 4 This is the HPLC chart of the final product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate prepared in Example 1 of the present invention. Detailed Description of the Invention

[0027] To better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

[0028] Unless otherwise specified, the experimental methods used in the examples of the present invention are all conventional methods.

[0029] Unless otherwise specified, the materials, reagents, etc. used in the examples of the present invention can all be obtained from commercial sources.

[0030] The following examples are intended to illustrate the present invention rather than further limit the present invention.

[0031] Example 1

[0032] (1) First, 412.5 L of toluene solvent was added to the reactor, and then 3-N,N-diethylaminophenol (82.5 kg, 5 mol) and phthalic anhydride (74 kg, 5 mol) were added. Under the action of (15.8 kg, 1 mol) of silica-supported sulfuric acid catalyst (H 2 SO 4 -SiO 4 ), the reaction was refluxed for 4 h to carry out the Friedel-Crafts acylation reaction to generate 2-hydroxy-4-diethylamino-2'-carboxybenzophenone; after the reflux reaction, 330 L of toluene solvent was recovered by heating and refluxing at 110 °C.

[0033] (2) Subsequently, n-hexanol (132 kg, 15 mol) was added to the reaction solution in step (1), and the reaction was continued to reflux for 6 h to carry out the esterification reaction to generate hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate.

[0034] (3) After the reflux reaction, the catalyst was recovered by hot filtration and reused for the synthesis reaction. The filtrate was transferred to a stripping kettle to recover toluene under reduced pressure. After cooling crystallization and filtration, 178 kg of light purple-red primary refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate was obtained (as Figure 1 shown: The product content was detected by HPLC isocratic method to be 96.28%);

[0035] After the primary refined mother liquor was concentrated under reduced pressure, 22 kg of concentrated mother liquor of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate was obtained (as Figure 2 shown: The product content was detected by HPLC isocratic method to be 57.44%); 5 kg of sodium hydroxide and 100 kg of water were added to the concentrate and put into a reactor, and the reaction was carried out at 80 °C for 6 h. Then the system was separated by water. The lower aqueous phase was adjusted to pH 5 with sulfuric acid, and a large amount of earth-yellow solid was precipitated in the aqueous phase. After filtration and drying, 7.5 kg of 2-hydroxy-4-diethylamino-2'-carboxybenzophenone was obtained (as Figure 3 shown: The intermediate content was detected by HPLC isocratic method to be 93.23%), which was used for the reaction in step (2); The organic phase was distilled to recover n-hexanol produced by hydrolysis.

[0036] (4) 178 kg of the primary refined product was de-n-hexanolized under reduced pressure at 100 °C, 356 kg of anhydrous ethanol and 20 kg of activated carbon were added, and the mixture was refluxed for decolorization for 1 h, filtered, cooled and crystallized, and the product was obtained by centrifugal filtration. 149 kg of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate was obtained through a freeze dryer (as Figure 4 shown: The product content was detected by HPLC gradient method for finished products to be 99.09%), and the single-pass yield was 75%.

[0037] Example 2

[0038] (1) First, 825 L of toluene solvent was added to the reactor, and then 3-N,N-diethylaminophenol (165 kg, 10 mol) and phthalic anhydride (148 kg, 10 mol) were added. Under the action of (32 kg, 2 mol) of silica-supported sulfuric acid catalyst (H 2 SO 4 -SiO 4 ), the reflux reaction was carried out for 6 h, and the Friedel-Crafts acylation reaction occurred to generate 2-hydroxy-4-diethylamino-2'-carboxybenzophenone; After the reflux reaction, 660 L of toluene solvent was recovered by heating and refluxing at 110 °C.

[0039] (2) Subsequently, n-hexanol (264 kg, 30 mol) was added to the reaction solution in step (1), and the reflux reaction was continued for 8 h to carry out an esterification reaction to produce hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate.

[0040] (3) After the reflux reaction, the catalyst was recovered by hot filtration while it was hot. The filtrate was transferred to a stripping kettle to recover toluene under reduced pressure. After cooling crystallization and filtration, 349 kg of a light purple-red primary refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content 96.52%) was obtained;

[0041] The mother liquor of the primary refinement was concentrated under reduced pressure to obtain 52 kg of a concentrate of the mother liquor of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content 57.45%); 20 kg of sodium carbonate and 200 kg of water were added to the concentrate and put into a reactor, and the reaction was carried out at 100 °C for 24 h. Then, the system was separated by water. The lower aqueous phase was adjusted to pH 5 with sulfuric acid, and a large amount of earthy yellow solid precipitated out in the aqueous phase. After filtration and drying, 18 kg of 2-hydroxy-4-diethylamino-2'-carboxybenzophenone (HPLC content 93.64%) was obtained.

[0042] (4) The 349 kg of the primary refined product was de-evaporated of n-hexanol under reduced pressure at 100 °C, 700 kg of absolute ethanol and 40 kg of activated carbon were added, and the mixture was refluxed for decolorization for 1 h, filtered, cooled for crystallization, and centrifugally filtered to obtain the product. 293 kg of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content 99.12%) was obtained through a freeze dryer, and the single-pass yield was 74%.

[0043] Example 3

[0044] (1) First, 990 L of toluene solvent was added to a reactor, and then 3-N,N-diethylaminophenol (198 kg, 12 mol) and phthalic anhydride (178 kg, 12 mol) were added. Under the action of a silica gel-supported sulfuric acid catalyst (H 2 SO 4 -SiO 4 ), the reflux reaction was carried out for 6 h to carry out a Friedel-Crafts acylation reaction to produce 2-hydroxy-4-diethylamino-2'-carboxybenzophenone; after the reflux reaction, 950 L of toluene solvent was recovered by heating and refluxing at 110 °C.

[0045] (2) Subsequently, n-hexanol (318 kg, 36 mol) was added to the reaction solution in step (1), and the reflux reaction was continued for 6 h to carry out an esterification reaction to produce hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate.

[0046] (3) After the reflux reaction, 42 kg of the catalyst was recovered by hot filtration while it was still hot. The filtrate was transferred to a stripping kettle to recover toluene under reduced pressure. After cooling crystallization and filtration, 433 kg of light purple-red primary refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content 96.56%) was obtained;

[0047] The primary refined mother liquor was concentrated under reduced pressure to obtain 46 kg of concentrated mother liquor of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content 58.63%); 18 kg of potassium hydroxide and 200 kg of water were added to this concentrate and put into a reactor. The reaction was carried out at 80 °C for 8 h, and then the system was separated from water. The lower aqueous phase was adjusted to pH 5 with sulfuric acid, and a large amount of earthy yellow solid precipitated out in the aqueous phase. After filtration and drying, 14 kg of 2-hydroxy-4-diethylamino-2'-carboxybenzophenone (content 94.57%) was obtained.

[0048] (4) 433 kg of the primary refined product was deodorized with n-hexanol under reduced pressure at 100 °C, 850 kg of absolute ethanol and 50 kg of activated carbon were added, and the mixture was refluxed for decolorization for 1 h. After filtration, cooling crystallization, and centrifugal filtration, the product was obtained. 362 kg of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content 99.13%) was obtained through a freeze dryer, and the single-pass yield was 76%.

[0049] Example 4

[0050] (1) First, 1238 L of toluene solvent was added to the reactor, and then 3-N,N-diethylaminophenol (248 kg, 15 mol) and phthalic anhydride (222 kg, 15 mol) were added. Newly added (16 kg, 1 mol) silica-supported sulfuric acid catalyst (H 2 SO 4 -SiO 4 ) was added. Under the action of the recovered catalyst in Example 2 (42 kg, theoretical amount 2.4 mol), the reflux reaction was carried out for 6 h, and the Friedel-Crafts acylation reaction occurred to generate 2-hydroxy-4-diethylamino-2'-carboxybenzophenone; after the reflux reaction, 990 L of toluene solvent was recovered by heating and refluxing at 110 °C.

[0051] (2) Subsequently, n-hexanol (396 kg, 45 mol) was added to the reaction solution in step (1), and the reflux reaction was continued for 6 h to carry out the esterification reaction to generate hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate.

[0052] (3) After the reflux reaction, filter while it is hot to recover the catalyst. Transfer the filtrate to a stripping kettle to recover toluene under reduced pressure. Cool and crystallize, then filter to obtain 537 kg of light purplish-red primary refined product of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content: 97.23%);

[0053] The primary refined mother liquor is concentrated under reduced pressure to obtain 64 kg of concentrated mother liquor of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content: 62.86%); Put this concentrate, 20 kg of potassium carbonate, and 200 kg of water into a reactor, then separate the water in the system. Adjust the pH of the lower aqueous phase to 5 with sulfuric acid. A large amount of khaki solid precipitates in the aqueous phase. Filter and dry to obtain 21 kg of 2-hydroxy-4-diethylamino-2'-carboxybenzophenone (HPLC content: 93.14%).

[0054] (4) Evacuate n-hexanol from 537 kg of the primary refined product at 100 °C under reduced pressure. Add 1000 kg of absolute ethanol and 60 kg of activated carbon, reflux and decolorize for 1 h, filter, cool and crystallize, and then centrifuge and filter to obtain the product. Obtain 465 kg of hexyl 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoate (HPLC content: 98.86%) through a freeze dryer, and the single-pass yield is 78%.

[0055] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A process for synthesizing 2-(4-N,N-diethylamino-2-hydroxybenzoyl) benzoic acid hexyl ester, characterized in that: The following steps are involved: (1) Using a solid acid as a catalyst, 3-N,N-diethylaminophenol and phthalic anhydride are added to an organic solvent, refluxed to react, and Friedel-Crafts acylation reaction occurs to generate 2-hydroxy-4-diethylamino-2'-carboxybenzophenone; after the reflux reaction, the organic solvent is recovered; the catalyst is a sulfuric acid catalyst supported by silica gel; the organic solvent is at least one of toluene and xylene, and the solid-liquid ratio of 3-N,N-diethylaminophenol to the organic solvent is 1:4-7 in kg / L; the molar ratio of 3-N,N-diethylaminophenol, phthalic anhydride, catalyst, and n-hexanol is 1:0.8-1.2:0.01-0.3:2-4; (2) Then, n-hexanol is added to the reaction solution of step (1) to react with the 2-hydroxy-4-diethylamino-2'-carboxybenzophenone to produce 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl ester through an esterification reaction; (3) Then, the catalyst is recovered by hot filtration, the filtrate is decompressed to recover the organic solvent, cooled, crystallized, and filtered to obtain a primary refined product of 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl ester; The first refined mother liquor is concentrated under reduced pressure to obtain a refined mother liquor concentrate; the refined mother liquor concentrate is reacted with alkali and water at 80-100° C. for 6-8 hours, and then the system is separated, sulfuric acid is added to the lower aqueous phase to adjust the pH to 4-6 and filtered to obtain 2-hydroxy-4-diethylamino-2'-carboxybenzophenone, and the organic phase is distilled to recover the n-hexanol produced by hydrolysis; The alkali is at least one of sodium hydroxide, sodium carbonate, potassium hydroxide or potassium carbonate; the weight of the alkali is 20%-40% of the weight of the refined mother liquor concentrate; (4) The first refined product is subjected to reduced pressure to recover n-hexanol, and then subjected to secondary refinement using ethanol as solvent, followed by decolorization, filtration, cooling crystallization, centrifugation, and drying to obtain the target 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl ester.

2. The synthesis process of 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl ester according to claim 1, characterized in that: Step (2), the reaction time is 6-10 h.

3. The synthesis process of 2-(4-N,N-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl ester according to claim 1, characterized in that: In step (4), the decolorization is performed by adding activated carbon for reflux decolorization, the reflux time is 0.8-1.2 hours, and the mass ratio of the primary refined product to ethanol and activated carbon is 1:1.5-2.5:0.11-0.12; and the drying is freeze-drying.

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