Preparation method of isooctyl p-aminobenzoate

Abstract

The invention discloses a preparation method of isooctyl p-aminobenzoate. The preparation method comprises the following steps: carrying out esterification reaction on p-nitrobenzoic acid and isooctyl alcohol in the presence of a catalyst and a water-carrying agent to obtain an intermediate isooctyl p-nitrobenzoate; and performing catalytic hydrogenation on the intermediate isooctyl p-nitrobenzoate to obtain the target product isooctyl p-aminobenzoate. A rectifying column is arranged in a reaction device adopted by the esterification reaction. The rectifying column is arranged in the esterification reaction device, so that the water removal efficiency can be effectively improved, the reaction time can be greatly shortened, the product purity can be effectively improved, and the product quality can be improved; besides, the acidic ionic liquid is adopted as the esterification reaction catalyst, so that a better catalytic effect can be obtained, a higher reaction yield is obtained, the catalyst can be recycled and reused through liquid phase layering operation, the activity of the recycled catalyst is kept well, and the operation is simple.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals, and in particular relates to a method for preparing isooctyl p-aminobenzoate. Background Art

[0002] Triazine UV absorbers are a new type of highly efficient and broad-spectrum UV absorbers that have been developed in recent years. They have a large molecular structure, high UV absorption efficiency and antioxidant function, and are the development direction of UV absorbers. As a new type of triazine UV absorber, octyl triazone has a large molecular structure and high UV absorption efficiency, has a spectrum sunscreen effect, and is the oil-soluble absorber with the strongest UV-B absorption capacity on the market today. It has high light stability and prevents UV-B-induced immunosuppression, has strong water resistance, and has good affinity with skin keratin. As a sunscreen, octyl triazone has the advantages of high absorption rate and low addition amount. Usually, in sunscreen care products, only a very small dose is needed to achieve a higher SPF value and have excellent sunscreen effect.

[0003] Isooctyl p-aminobenzoate (also known as PABA ethylhexyl ester) is an important raw material for the synthesis of octyl triazone. Its CAS number is 26218-04-2 and its molecular formula is C 15 H 23 NO2, molecular weight is 249.35.

[0004] Chinese patent document CN104860893A discloses a method for synthesizing an ultraviolet absorber octyl triazone, which uses sodium bisulfate as a catalyst, and in the presence of toluene, esterifies p-nitrobenzoic acid and isooctyl alcohol to obtain an intermediate p-nitrobenzoic acid isooctyl ester, which is then reduced to p-aminobenzoic acid isooctyl ester by iron powder / ammonium chloride in a methanol-water solution.

[0005] The shortcomings of this method are: (1) The catalyst used in the esterification reaction is not effective, the reaction yield is only about 90%, and the total yield of the two-step reaction is only 80-85%. (2) The hydrogenation reaction uses iron powder as a reducing agent, which causes great environmental pollution.

[0006] Chinese patent document CN112321522A discloses a method for preparing a sunscreen agent octyl triazone, which comprises the following steps: esterifying p-nitrobenzoic acid and isooctyl alcohol (serving as both a reaction raw material and a water-carrying agent) in the presence of a catalyst, p-toluenesulfonic acid, to obtain an intermediate isooctyl p-nitrobenzoate; and catalytically hydrogenating the intermediate isooctyl p-nitrobenzoate to obtain a target product, isooctyl p-aminobenzoate.

[0007] The disadvantages of this method are: (1) a large amount of isooctyl alcohol is required, which not only increases the production cost but also makes the post-processing complicated. (2) The product purity is low, less than 99.6%. Summary of the invention

[0008] The object of the present invention is to solve the above problems and provide a method for preparing isooctyl p-aminobenzoate with short reaction time and high product purity.

[0009] The technical scheme for achieving the purpose of the present invention is: a method for preparing isooctyl p-aminobenzoate, comprising an esterification reaction of p-nitrobenzoic acid and isooctyl alcohol in the presence of a catalyst and a water-carrying agent to obtain an intermediate isooctyl p-nitrobenzoate; and catalytic hydrogenation of the intermediate isooctyl p-nitrobenzoate to obtain the target product isooctyl p-aminobenzoate; characterized in that a distillation column is provided in the reaction device used in the esterification reaction.

[0010] The molar ratio of the p-nitrobenzoic acid to the isooctyl alcohol is 1:1 to 1:1.2.

[0011] The water-carrying agent is one or more of benzene, toluene, xylene, n-heptane and cyclohexane.

[0012] The dosage of the water-carrying agent is 1 to 3 times the weight of the p-nitrobenzoic acid.

[0013] In order to improve the reaction yield, the esterification reaction uses an acidic ionic liquid as a catalyst.

[0014] The acidic ionic liquid is 1-butylsulfonic acid-3-methylimidazole p-toluenesulfonate or N-methylpyrrolidone hydrogen sulfate; the amount of the acidic ionic liquid is 0.5-1.5% of the total weight of the p-nitrobenzoic acid and isooctyl alcohol.

[0015] The catalyst used in the catalytic hydrogenation is a noble metal catalyst, preferably a platinum group metal catalyst or a nickel metal catalyst, more preferably one of platinum / carbon, palladium / carbon and ruthenium / carbon catalysts.

[0016] The reaction temperature of the catalytic hydrogenation is 50-150° C., and the reaction pressure is 0.5-1.5 MPa.

[0017] The present invention has the positive effects: (1) The present invention installs a distillation column in the esterification reaction device, which can not only effectively improve the water removal efficiency and greatly reduce the reaction time, but also effectively improve the product purity (above 99.9%), thereby greatly improving the product quality.

[0018] (2) The present invention uses an acidic ionic liquid as an esterification reaction catalyst, which can not only achieve a good catalytic effect and thus a higher reaction yield (the two-step reaction yield can reach more than 95%), but also the catalyst can be recovered and reused through liquid phase stratification operation, and the activity of the recovered catalyst is well maintained, and the operation is simple. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The DSC spectrum of the final product obtained in Example 1 is shown in FIG.

[0020] Figure 2 The ESI-MS spectrum of the final product obtained in Example 1 is shown in FIG. DETAILED DESCRIPTION

[0021] (Example 1) The preparation method of isooctyl p-aminobenzoate of the present embodiment comprises the following steps: ① Esterification reaction.

[0022] At room temperature, 400 mL of n-heptane, 180 g (1.08 mol) of p-nitrobenzoic acid, 147.3 g (1.13 mol) of isooctyl alcohol and 3.0 g of 1-butylsulfonic acid-3-methylimidazole p-toluenesulfonate were added to a 1 L reaction bottle equipped with a short distillation column (insulated with heat-insulating cotton, with a water separator connected to the upper end) and the temperature was raised to reflux for water separation reaction. The reaction was complete after about 2 hours.

[0023] After the reaction was completed, the temperature was lowered, the layers were separated, the catalyst in the lower layer was recovered and reused, the upper organic layer was washed with 90 mL of water, the layers were separated, and the organic layer was directly used for the next step reaction.

[0024] ②Catalytic hydrogenation reaction.

[0025] Add the organic layer obtained in step ① to a 1L autoclave, and add 12.5g, 5wt% palladium carbon catalyst at the same time, seal the autoclave, replace the air with nitrogen 3 times, then replace the nitrogen with hydrogen 3 times, and adjust the hydrogen pressure to 0.8-1.0MPa, then raise the temperature to 100-110°C, and carry out catalytic hydrogenation reaction to completion.

[0026] After the reaction, the hydrogen in the kettle was replaced with nitrogen, the filter was filtered, the catalyst was used, the filtrate was cooled to 10-20°C, stirred for 1h, filtered, the filter cake was washed with a small amount of n-heptane, and vacuum dried to obtain 261.3g of off-white solid with a yield of 97.3%, a purity of 99.95% (HPLC), and a melting point of 54.39°C (see Figure 1 ).

[0027] The ESI-MS spectrum of the final product is shown in Figure 2 ,Depend on Figure 2 It can be seen that its molecular weight is 249.0 (M+H), which is consistent with that of isooctyl p-aminobenzoate.

[0028] (Comparative Example 1) The preparation method of isooctyl p-aminobenzoate of this comparative example comprises the following steps: ① Esterification reaction.

[0029] At room temperature, 400 mL of n-heptane, 180 g (1.08 mol) of p-nitrobenzoic acid, 147.3 g (1.13 mol) of isooctyl alcohol and 3.0 g of 1-butylsulfonic acid-3-methylimidazole p-toluenesulfonate were added to a 1 L reaction bottle (the upper end of which was connected to a water separator, but no distillation column was installed between the reaction bottle and the water separator), and the temperature was raised to reflux for water separation reaction. The reaction was complete after about 3.5 hours.

[0030] After the reaction was completed, the temperature was lowered, the layers were separated, the catalyst in the lower layer was recovered and reused, the upper organic layer was washed with 90 mL of water, the layers were separated, and the organic layer was directly used for the next step reaction.

[0031] ②Catalytic hydrogenation reaction.

[0032] Add the organic layer obtained in step ① to a 1L autoclave, and add 12.5g, 5wt% palladium carbon catalyst at the same time, seal the autoclave, replace the air with nitrogen 3 times, then replace the nitrogen with hydrogen 3 times, and adjust the hydrogen pressure to 0.8-1.0MPa, then raise the temperature to 100-110°C, and carry out catalytic hydrogenation reaction to completion.

[0033] After the reaction, the hydrogen in the kettle was replaced with nitrogen, the mixture was filtered, the catalyst was applied, the filtrate was cooled to 10-20°C, stirred for 1 hour, filtered, the filter cake was washed with a small amount of n-heptane, and vacuum dried to obtain 257.3 g of off-white solid isooctyl p-aminobenzoate with a yield of 95.8%, a purity of 99.77% (HPLC), and a melting point of 54.16°C.

[0034] (Example 2) The preparation method of isooctyl p-aminobenzoate of the present embodiment comprises the following steps: ① Esterification reaction.

[0035] At room temperature, 400 mL of xylene, 180 g (1.08 mol) of p-nitrobenzoic acid, 147.3 g (1.13 mol) of isooctyl alcohol and 3.2 g of 1-butylsulfonic acid-3-methylimidazole p-toluenesulfonate were added to a 1 L reaction bottle equipped with a short distillation column (insulated with heat-insulating cotton, with a water separator connected to the upper end) and the temperature was raised to reflux for water separation reaction. The reaction was complete after about 1.5 h.

[0036] After the reaction was completed, the temperature was lowered, the layers were separated, the catalyst in the lower layer was recovered and reused, the upper organic layer was washed with 90 mL of water, the layers were separated, and the organic layer was directly used for the next step reaction.

[0037] ②Catalytic hydrogenation reaction.

[0038] Add the organic layer obtained in step ① to a 1L autoclave, and add 12.5g, 5wt% palladium carbon catalyst at the same time, seal the autoclave, replace the air with nitrogen 3 times, then replace the nitrogen with hydrogen 3 times, and adjust the hydrogen pressure to 0.8-1.0MPa, then raise the temperature to 100-110°C, and carry out catalytic hydrogenation reaction to completion.

[0039] After the reaction, the hydrogen in the kettle was replaced with nitrogen, the mixture was filtered, the catalyst was applied, the filtrate was cooled to 10-20°C, stirred for 1h, filtered, the filter cake was washed with a small amount of xylene, and vacuum dried to obtain 260.5g of off-white solid isooctyl p-aminobenzoate with a yield of 97.0%, a purity of 99.92% (HPLC), and a melting point of 54.33°C.

[0040] (Example 3) The preparation method of isooctyl p-aminobenzoate of the present embodiment comprises the following steps: ① Esterification reaction.

[0041] At room temperature, 450 mL of toluene, 200 g (1.20 mol) of p-nitrobenzoic acid, 163.7 g (1.25 mol) of isooctyl alcohol and 3.2 g of N-methylpyrrolidone hydrogen sulfate were added to a 1 L reaction flask equipped with a short distillation column (insulated with heat-insulating cotton, with a water separator connected to the upper end) and the temperature was raised to reflux for water separation reaction. The reaction was complete after about 2 hours.

[0042] After the reaction is completed, the temperature is lowered, the layers are separated, the catalyst in the lower layer is recovered and reused, the upper organic layer is washed with 100 mL of water, the layers are separated, and the organic layer is directly used for the next step reaction.

[0043] ②Catalytic hydrogenation reaction.

[0044] Add the organic layer obtained in step ① to a 1L autoclave, and add 13.5g, 5wt% palladium carbon catalyst at the same time, seal the autoclave, replace the air with nitrogen 3 times, then replace the nitrogen with hydrogen 3 times, and adjust the hydrogen pressure to 0.7-1.0MPa, then raise the temperature to 100-110°C, and carry out catalytic hydrogenation reaction to completion.

[0045] After the reaction, the hydrogen in the kettle was replaced with nitrogen, the mixture was filtered, the catalyst was applied, the filtrate was cooled to 10-20°C, stirred for 1 hour, filtered, the filter cake was washed with a small amount of toluene, and vacuum dried to obtain 289.7 g of off-white solid isooctyl p-aminobenzoate with a yield of 97.1%, a purity of 99.95% (HPLC), and a melting point of 54.31°C.

[0046] (Example 4) The preparation method of isooctyl p-aminobenzoate of the present embodiment comprises the following steps: ① Esterification reaction.

[0047] At room temperature, 438 mL of toluene, 200 g (1.20 mol) of p-nitrobenzoic acid, 163.7 g (1.25 mol) of isooctyl alcohol and 3.5 g of 1-butylsulfonic acid-3-methylimidazole p-toluenesulfonate were added to a 1 L reaction bottle equipped with a short distillation column (insulated with heat-insulating cotton, with a water separator connected to the upper end) and the temperature was raised to reflux for water separation reaction. The reaction was complete after about 2 hours.

[0048] After the reaction is completed, the temperature is lowered, the layers are separated, the catalyst in the lower layer is recovered and reused, the upper organic layer is washed with 100 mL of water, the layers are separated, and the organic layer is directly used for the next step reaction.

[0049] ②Catalytic hydrogenation reaction.

[0050] Add the organic layer obtained in step ① to a 1L autoclave, and add 13.0g, 5wt% of palladium carbon catalyst at the same time, seal the autoclave, replace the air with nitrogen 3 times, then replace the nitrogen with hydrogen 3 times, and adjust the hydrogen pressure to 0.6-0.9MPa, then raise the temperature to 100-110°C, and carry out catalytic hydrogenation reaction to completion.

[0051] After the reaction, the hydrogen in the kettle was replaced with nitrogen, the filter was filtered, the catalyst was applied, the filtrate was cooled to 10-20°C, stirred for 1h, filtered, the filter cake was washed with a small amount of toluene, and vacuum dried to obtain 288.9g of off-white solid powder with a yield of 96.8%, a purity of 99.92% (HPLC), and a melting point of 54.29°C.

Claims

1. A method for preparing isooctyl p-aminobenzoate, comprising: subjecting p-nitrobenzoic acid and isooctyl alcohol to an esterification reaction in the presence of a catalyst and a water-carrying agent to obtain an intermediate isooctyl p-nitrobenzoate; and subjecting the intermediate isooctyl p-nitrobenzoate to catalytic hydrogenation to obtain the target product isooctyl p-aminobenzoate; characterized in that: The reaction device used in the esterification reaction is provided with a distillation column.

2. The method for preparing isooctyl p-aminobenzoate according to claim 1, wherein: The molar ratio of the p-nitrobenzoic acid to the isooctyl alcohol is 1:1 to 1:1.

2.

3. The method for preparing isooctyl p-aminobenzoate according to claim 1, wherein: The water-carrying agent is one or more of benzene, toluene, xylene, n-heptane and cyclohexane.

4. The method for preparing isooctyl p-aminobenzoate according to claim 3, wherein: The dosage of the water-carrying agent is 1 to 3 times the weight of the p-nitrobenzoic acid.

5. The method for preparing isooctyl p-aminobenzoate according to claim 1, wherein: The catalyst used in the catalytic hydrogenation is a noble metal catalyst.

6. The method for preparing isooctyl p-aminobenzoate according to claim 5, wherein: The noble metal catalyst is a platinum group metal catalyst or a nickel metal catalyst.

7. The method for preparing isooctyl p-aminobenzoate according to claim 1, wherein: The reaction temperature of the catalytic hydrogenation is 50-150° C., and the reaction pressure is 0.5-1.5 MPa.

8. The method for preparing isooctyl p-aminobenzoate according to any one of claims 1 to 7, characterized in that: The catalyst is an acidic ionic liquid.

9. The method for preparing isooctyl p-aminobenzoate according to claim 8, wherein: The acidic ionic liquid is 1-butylsulfonic acid-3-methylimidazolium p-toluenesulfonate or N-methylpyrrolidone hydrogen sulfate.

10. The method for preparing isooctyl p-aminobenzoate according to claim 8, wherein: The amount of the acidic ionic liquid used is 0.5-1.5% of the total weight of the p-nitrobenzoic acid and isooctyl alcohol.

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