Preparation method of 2-(4-hydroxybenzoyl) benzoic acid

Abstract

The invention discloses a preparation method of 2-(4-hydroxybenzoyl) benzoic acid, and belongs to the technical field of synthesis of organic intermediates. The method comprises the following steps: mixing phenol, phthalic acid, a water absorbent and a catalyst in hexafluoroisopropanol, and reacting under a heating condition to obtain 2-(4-hydroxybenzoyl) benzoic acid. The raw materials are available in the market, the HF complex is adopted as the catalyst and can be recycled, the catalytic efficiency is high, the phthalic anhydride is adopted as the water absorbent to absorb water generated after condensation of the phthalic acid, the activity of the catalyst is maintained, the phthalic anhydride reacts with the water to continuously generate the phthalic acid, and the phthalic acid can be continuously used as a raw material for reaction; the method is more environment-friendly.

Description

Technical Field

[0001] This invention relates to a method for preparing 2-(4-hydroxybenzoyl)benzoic acid, belonging to the field of organic intermediate synthesis technology. Background Technology

[0002] 2-(4-hydroxybenzoyl)benzoic acid (CAS No. 85-57-4) is an important chemical intermediate or raw material, mainly used in the preparation of polymer materials, organic intermediates, and catalyst supports. In the field of polymer materials: 2-(4-hydroxybenzoyl)benzoic acid undergoes a cyclization reaction with hydrazine hydrate to prepare 4-(4-hydroxyphenyl)phthalazine-1(2H)-one (DHPZ, CAS: 152594-70-2), which is the main monomer for the synthesis of polyarylether ketone (PPEK) polymers.

[0003]

[0004] There are two main synthetic routes for 2-(4-hydroxybenzoyl)benzoic acid: Patents and literature [European Journal of Organic Chemistry, 2017, 3274; WO 2006248 37A1; Journal of Medicinal Chemistry, 2006, 49, 6209; Chemistry - A European Journal, 2016, 22, 12363] use phenolphthalein as a raw material, reacting it with hydroxylamine hydrochloride and a base, followed by acidification to generate 2-(4-hydroxybenzoyl)benzoic acid; Patents and literature [CN118063390A; Research on Chemical Intermediates, 2019, 45, 2007; Journal of Enzyme Inhibition and Medicinal Chemistry, 2012, 27, 748; Journal of Medicinal Chemistry, [2004, 47, 2486] Using phthalic anhydride and phenol as raw materials, a Friedel-Crafts reaction occurs under the catalysis of aluminum trichloride to produce 2-(4-hydroxybenzoyl)benzoic acid.

[0005] Current synthetic methods suffer from drawbacks such as requiring expensive raw materials or generating numerous byproducts, and difficulty in purifying the product. Therefore, research and exploration of synthetic methods for 2-(4-hydroxybenzoyl)benzoic acid are needed to provide readily available and inexpensive raw materials and a simple and economical route, which can better reduce the cost of DHPZ / PPEK and broaden its application range. Summary of the Invention

[0006] This invention was made to solve the above-mentioned problems, and its purpose is to provide a preparation method with high yield and economical route.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: using phenol and phthalic acid as raw materials, 2-(4-hydroxybenzoyl)benzoic acid is synthesized in one step under the action of a catalyst and a dehydrating agent.

[0008] This invention provides a method for preparing 2-(4-hydroxybenzoyl)benzoic acid, comprising the following steps: Method A: Phenol, phthalic acid, desiccant and catalyst are mixed in hexafluoroisopropanol and reacted under heating conditions to obtain 2-(4-hydroxybenzoyl)benzoic acid; Method B: Phenol, phthalic acid, phthalic anhydride and trifluoromethanesulfonic acid are mixed in hexafluoroisopropanol and reacted at 50-80℃ to obtain 2-(4-hydroxybenzoyl)benzoic acid.

[0009] The synthetic route of this invention is represented by the following reaction equation:

[0010] Furthermore, under preferred conditions, in method A above, the desiccant is phthalic anhydride.

[0011] Furthermore, under preferred conditions, in method A above, the catalyst is Pyridine-9HF, DMPU-12HF, or KHSO4-13HF.

[0012] Furthermore, under preferred conditions, in method A above, the heating temperature is 20-50℃.

[0013] Furthermore, under preferred conditions, in method A above, the molar ratio of phenol, phthalic acid, desiccant and catalyst is 1:1-1.2:0.95-1.05:0.3-0.7.

[0014] Further, under preferred conditions, in method B above, the molar ratio of phenol, phthalic acid, phthalic anhydride and trifluoromethanesulfonic acid is 1:1.4-2:0.95-1.05:2-4.

[0015] The present invention has the following beneficial effects: 1. This invention uses inexpensive and readily available phenol and phthalic acid as raw materials to prepare 2-(4-hydroxybenzoyl)benzoic acid through a one-step reaction. The route is short, easy to operate, and has a high overall yield.

[0016] 2. In this invention, phthalic anhydride is used as a desiccant to absorb the water generated after the condensation of phthalic acid, thus maintaining the activity of the catalyst. At the same time, the reaction of phthalic anhydride with water continues to generate phthalic acid, which can be used as a raw material for further reaction. Excess phthalic acid can be recycled and reused, thus reducing costs.

[0017] 3. This invention uses HF complex as a catalyst, which can be recycled and reused, has high catalytic efficiency, and avoids the waste solids and low conversion rate generated by using aluminum trichloride catalyst. Specific Implementation The present invention will be further illustrated below with specific examples. These embodiments should be understood as illustrative only and not as limiting the scope of protection of the present invention. After reading the description of the present invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0019] Preparation of HF complexes (taking KHSO4-13HF preparation as an example): KHSO4 (2.72 g, 0.02 mol) was added to a tetrafluoroethylene reaction flask, cooled to 0 °C, and HF gas (5.28 g, 0.264 mol) was introduced into the reaction flask under stirring. The mixture was stirred for 20 min to obtain KHSO4-13HF (liquid). KHSO4-13HF was stored at 4 °C.

[0020] Example 1

[0021] Under nitrogen protection, phenol (9.4 g, 0.1 mol), phthalic acid (18.3 g, 0.11 mol), phthalic anhydride (14.8 g, 0.1 mol), and KHSO4-13HF (15.85 g, 0.04 mol) were mixed in 300 mL of hexafluoroisopropanol and reacted at 25 °C for 3 hours. The hexafluoroisopropanol was recovered by concentration at room temperature. The residue was slurried with ethanol, filtered, and the crude solid product was recrystallized from ethanol to give 22.3 g of 2-(4-hydroxybenzoyl)benzoic acid, with a yield of 92% and an HPLC resolution of 99.4%. 1 HN MR(400MHz, DMSO-d6): 10.39(s, 1H),7.95(d, 1H), 7.68(t, 1H), 7.61(t, 1H), 7.51(d, 2H), 7.32(d, 1H), 6.85(d, 2H)ppm.

[0022] Example 2

[0023] Under nitrogen protection, phenol (9.4 g, 0.1 mol), phthalic acid (18.3 g, 0.11 mol), phthalic anhydride (14.8 g, 0.1 mol), and DMPU-12HF (14.7 g, 0.04 mol) were mixed in 300 mL of hexafluoroisopropanol and reacted at 45 °C for 3 hours. The hexafluoroisopropanol was recovered by concentration at room temperature. The residue was slurried with ethanol, filtered, and the crude solid product was recrystallized from ethanol to give 21.1 g of 2-(4-hydroxybenzoyl)benzoic acid, with a yield of 87% and an HPLC purity of 99.2%.

[0024] Example 3

[0025] Under nitrogen protection, phenol (9.4 g, 0.1 mol), phthalic acid (18.3 g, 0.11 mol), phthalic anhydride (14.8 g, 0.1 mol), and pyridine-9HF (10.4 g, 0.04 mol) were mixed in 300 mL of hexafluoroisopropanol and reacted at 45 °C for 6 hours. The hexafluoroisopropanol was recovered by concentration at room temperature. The residue was slurried with ethanol, filtered, and the crude solid product was recrystallized from ethanol to give 19.4 g of 2-(4-hydroxybenzoyl)benzoic acid, with a yield of 80% and an HPLC resolution of 99.1%.

[0026] Example 4

[0027] Under nitrogen protection, phenol (9.4 g, 0.1 mol), phthalic acid (26.6 g, 0.16 mol), phthalic anhydride (14.8 g, 0.1 mol), and trifluoromethanesulfonic acid (45 g, 0.3 mol) were mixed in 300 mL of hexafluoroisopropanol and reacted at 70 °C for 10 hours. The hexafluoroisopropanol and trifluoromethanesulfonic acid were recovered by concentration at room temperature. The residue was slurried with ethanol, filtered, and the crude solid product was recrystallized from ethanol to give 20.6 g of 2-(4-hydroxybenzoyl)benzoic acid, with a yield of 85% and an HPLC resolution of 98.8%.

[0028] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing 2-(4-hydroxybenzoyl)benzoic acid, characterized in that, The process includes the following steps: Method A, mixing phenol, phthalic acid, a desiccant, and a catalyst in hexafluoroisopropanol and reacting them under elevated temperature to obtain 2-(4-hydroxybenzoyl)benzoic acid; Method B, mixing phenol, phthalic acid, phthalic anhydride, and trifluoromethanesulfonic acid in hexafluoroisopropanol and reacting them at 50-80°C to obtain 2-(4-hydroxybenzoyl)benzoic acid.

2. The method for preparing 2-(4-hydroxybenzoyl)benzoic acid according to claim 1, characterized in that: In method A, the absorbent is phthalic anhydride.

3. The method for preparing 2-(4-hydroxybenzoyl)benzoic acid according to claim 1, characterized in that: In Method A, the catalyst is selected from Pyridine-9HF, DMPU-12HF, or KHSO4-13HF.

4. The method for preparing 2-(4-hydroxybenzoyl)benzoic acid according to claim 1, characterized in that: In Method A, the heating conditions are 20-50℃.

5. The method for preparing 2-(4-hydroxybenzoyl)benzoic acid according to claim 1, characterized in that: In method A, the molar ratio of phenol, phthalic acid, desiccant and catalyst is 1:1-1.2:0.95-1.05:0.3-0.

7.

6. The method for preparing 2-(4-hydroxybenzoyl)benzoic acid according to claim 1, characterized in that: In method B, the molar ratio of phenol, phthalic acid, phthalic anhydride and trifluoromethanesulfonic acid is 1:1.4-2:0.95-1.05:2-4.

Images