Preparation method of 2-hydroxy-5-aminobenzoic acid

A technology of aminobenzoic acid and aminobenzoate, applied in the preparation of organic compounds, chemical instruments and methods, cyanide reaction preparation, etc., can solve the problems of serious pollution of three wastes, difficult purification, unknown catalyst, etc., and achieve HPLC purity Good, easy to obtain raw materials, low cost effect

Active Publication Date: 2014-06-25
ZHEJIANG HUAHAI PHARMACEUTICAL CO LTD
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Problems solved by technology

[0003] The synthesis of bibliographical information 2-hydroxyl-5-aminobenzoic acid mainly contains following three kinds of methods at present: (1) aniline synthesis method, this method is starting material with aniline, through diazotization, coupling and reduction obtain again, and this route is relatively long, low yield
In addition, aniline is highly toxic, and it is easy to be brought into the finished product, it is not easy to be refined and removed, and it is also harmful to the environment; (2) Nitrosalicylic acid reduction method, which uses salicylic acid as the starting material, first Nitric acid is nitrated to obtain 5-nitrosalicylic acid, and then the nitro group is reduced to amino with iron powder under acidic conditions. After treatment, 2-hydroxyl-5-aminobenzoic acid is precipitated under weakly acidic conditions. The total yield of this route is about 50%, the route is simple, but easy to produce isomers in the nitration process, resulting in difficult purification in the later stage, because a large amount of nitric acid and iron powder are used in the reaction, the three wastes pollution is more serious; (3) Kolbe-Schmitt synthesis method, this method is React with carbon dioxide under high temperature and pressure to generate 2-hydroxy-5-aminobenzoic acid
Utilize this method, Chinese Journal of Pharmaceutical Industry, 1997,28 (8), people such as 341-342 Mo Fen Zhu have reported to take p-aminophenol as raw material, react with carbon dioxide under high temperature and high pressure, although this process route is brief, yield is high, However, the catalyst is unknown, and the aftertreatment is cumbersome, whi...

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  • Preparation method of 2-hydroxy-5-aminobenzoic acid

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Experimental program
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Effect test

Embodiment 1

[0025] Embodiment 1: add 16g p-aminophenol, 43g NaCl, 47g Na in autoclave 2 CO 3 , After the feeding is completed, replace the reaction vessel with carbon dioxide gas three times, then press it to 1.0MPa, slowly raise the temperature to 200°C, and react at this temperature for 6 hours. After the reaction is finished, cool down to 50°C, release the pressure and open the reaction kettle, add 200mL sodium dithionite solution into the reaction kettle, stir for another 1-2 hours, filter out the insoluble matter, and adjust the pH of the filtrate to 1.0-6.0 with hydrochloric acid , a solid was precipitated, filtered to obtain a gray solid crude product. The crude product was slurried in water to obtain an off-white solid with a yield of 90% and a purity of 99.1%; melting point: 279-281° C. (dec).

[0026] 1 H NMR (400MHz, DMSO-d 6 ): δ=7.12(s, 1H, ArH), 6.86-6.83(m, 1H, ArH), 6.68(d, 1H, J=8.8Hz, ArH).

Embodiment 2

[0027] Embodiment 2: add 16g p-aminophenol, 11g KCl, 20g K in autoclave 2 CO 3 , After the feeding is completed, replace the reaction vessel with carbon dioxide gas three times, then press it to 3.0MPa, slowly raise the temperature to 180°C, and react at this temperature for 6 hours. After the reaction is finished, cool down to 50°C, release the pressure and open the reaction kettle, add 200mL sodium dithionite solution into the reaction kettle, stir for 1-2 hours, filter out the insoluble matter, and adjust the pH of the filtrate to 1.0-6.0 with acid , a solid was precipitated, filtered to obtain a gray solid crude product. The crude product was slurried in water to obtain an off-white solid with a yield of 88% and a purity of 99.3%.

Embodiment 3

[0028] Embodiment 3: add 16g p-aminophenol, 163g KCl, 162g K in autoclave 2 CO 3 , After the feeding is completed, replace the reaction vessel with carbon dioxide gas three times, then press it to 1.5MPa, slowly raise the temperature to 220°C, and react at this temperature for 6 hours. After the reaction is finished, cool down to 50°C, release the pressure and open the reaction kettle, add 200mL sodium dithionite solution into the reaction kettle, stir for 1-2 hours, filter out the insoluble matter, and adjust the pH of the filtrate to 1.0-6.0 with acid , a solid was precipitated, filtered to obtain a gray solid crude product. The crude product was slurried in water to obtain an off-white solid with a yield of 86% and a purity of 99.5%.

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Abstract

The invention provides a preparation method of 2-hydroxy-5-aminobenzoic acid, comprises the following steps: carrying out Kolbe-Schmitt reaction on p-aminophenol as an initial raw material to obtain the target compound with high yield under the effect of a catalytic carrier or solid alkali or under the direct catalytic carrier effect on the p-aminophenol. The path is simple and short, the used catalytic carrier is capable of improving the heat transfer effect, reducing the energy consumption and improving the yield. Furthermore, the catalytic carrier is non-wear to the equipment, the security is improved, the purifying treatment is convenient, and the preparation method is suitable for the industrial production.

Description

technical field [0001] The invention belongs to the synthesis of organic compounds, and mainly relates to a method for preparing 2-hydroxyl-5-aminobenzoic acid by Kolbe-Schmitt reaction catalysis. technical background [0002] 2-Hydroxy-5-aminobenzoic acid (or 5-aminosalicylic acid) is an important medicine and dye intermediate, and it also has medicinal properties. It was approved by the US FDA as early as 1981 for the treatment of colon The drug of choice for inflammation, the drug name is Mesalazine (Mesalazine). 2-Hydroxy-5-aminobenzoic acid can carry out various reactions due to the three active reactive groups of amino, hydroxyl and carboxyl on the ring. Therefore, in the dye industry, it can be used to manufacture a variety of reactive dyes with excellent quality. [0003] The synthesis of bibliographical information 2-hydroxyl-5-aminobenzoic acid mainly contains following three kinds of methods at present: (1) aniline synthesis method, this method is starting mater...

Claims

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Application Information

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IPC IPC(8): C07C229/64C07C227/02
Inventor 刘洋荣乐义张文灵王鹏陈健陈曦
Owner ZHEJIANG HUAHAI PHARMACEUTICAL CO LTD
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