Preparation method of 2-hydroxy-5-aminobenzoic acid

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...

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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, which brings inconvenience to the production; Indian patent IN2004MU01242 reports that paracetamol is used as the starting material, and under high temperature and pressure, the carboxylation reaction is carried out in the presence of solid alkali and carbon dioxide. The reaction time is longer, the energy consumption is higher, and the gas-solid two-phase reaction is not well contacted, and the reaction material is easily localized and charred; CN102126977 has invented a gas-phase catalytic carboxylation method to prepare 5-aminosalicylic acid. Carbon dioxide is introduced into the aminophenol and basic compound system, but the process uses a catalytic carrier, and the catalytic carrier silicon oxide, molecular sieve, aluminum oxide, quartz sand and diatomaceous earth may wear the reactor wall to a certain extent, and the high-pressure In terms of reaction, the risk increases; CN102731334 discloses a method for preparing 5-aminosalicylic acid: dissolving sodium p-aminophenate in chlorinated 1-butyl-3-methylimidazolium ionic liquid, and then injecting The liquid is passed into carbon dioxide gas, and reacted at a pressure of 0.5-3MPa and a temperature of 120-200°C to obtain 5-aminosalicylic acid

However, the method uses ionic liquids to increase the reaction cost and the hygroscopicity of sodium p-aminophenate is too strong, which is not conducive to large-scale production; finally Asian J.Chem., 2011, 23 (9), pp3819-3823 reports the use of supercritical CO 2 A method for preparing 5-aminosalicylic acid from gas, but this method needs to react for 2.5 hours at a high temperature of 140°C, a high pressure of 9.0Mpa, and a high speed of 300rpm

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