Preparation method of 2-amino-3-nitrobenzoic acid

Abstract

The invention provides a preparation method of 2-amino-3-nitrobenzoic acid. The method comprises the following steps: performing Curtius rearrangement reaction on 3-nitrophthalic acid as a raw material to obtain 2-amino-3-nitrobenzoic acid with high yield, wherein the yield of 2-amino-3-nitrobenzoic acid is increased by more than 10% in comparison with that of 2-amino-3-nitrobenzoic acid in an existing process. Compared with the existing process, the method is easy to widely popularize industrially. According to the solution, 3-nitrophthalic acid serving as the raw material is subjected to mono-esterification, acylating chlorination and Curtius rearrangement hydrolyzation to obtain 2-amino-3-nitrobenzoic acid with the yield of 95%.

Description

technical field

[0001] The invention relates to a preparation method of 2-amino-3-nitrobenzoic acid widely used in the synthesis and preparation of medicines, pesticides and various functional materials. Background technique

[0002] 2-Amino-3-nitrobenzoic acid is an important intermediate in organic synthesis, used in the synthesis of pesticides and various functional materials, and also in the synthesis of benzimidazole drugs candesartan, azilsartan, ABT- 472 Key intermediates of PAPR inhibitors.

[0003] The synthesis of 2-amino-3-nitrobenzoic acid, the relevant patent documents are as follows:

[0004] 1. U.S. patent: US2005 020 626, using 2-chloro-3-nitrobenzoic acid as raw material to obtain 2-amino-3-nitrobenzoic acid through ammonolysis.

[0005] 2. Japanese patent: JP2001 163 843, using 7-nitroisatin as raw material, undergoing oxidation and alkaline hydrolysis under alkaline conditions to obtain 2-amino-3-nitrobenzoic acid.

[0006] 3. There are public documents...

Examples

Embodiment 1

[0058] Embodiment 1: the preparation of 2-amino-3-nitrobenzoic acid methyl ester:

[0059] ①.Monoesterification (preparation of 2-carboxy-3-nitrobenzoic acid methyl ester);

[0060]600ml of anhydrous methanol, 100g of 3-nitrophthalic acid, 50ml of concentrated sulfuric acid, heated to reflux, followed by liquid chromatography to control the end point of the reaction, and crystallized at 0°C to obtain the monoesterification product: 2-carboxy-3-nitrobenzene Methyl formate, dried product 90.4g, purity 98.8%, Mp160.4~161℃ (document Mp160~162℃).

[0061] ②. Acyl chloride;

[0062] Add 300ml of chloroform and 50g of thionyl chloride to the monoesterification product (dried product), reflux reaction, and lower the temperature to obtain a solution of acid chloride.

[0063] ③.Curtius heavy discharge hydrolysis;

[0064] To the solution of acid chloride, add 35g of sodium azide, react at room temperature, follow and control the reaction end point by liquid chromatography, after the...

Embodiment 2

[0065] Embodiment 2: the preparation of 2-amino-3-nitrobenzoic acid:

[0066] Add 60g of methyl 2-amino-3-nitrobenzoate, add 300ml of water and 15g of sodium hydroxide, heat to reflux, follow the liquid chromatography to control the end point of the reaction, complete hydrolysis, lower the temperature, add hydrochloric acid dropwise, adjust the pH to 2-3, and crystallize on cooling , to get 54.5g of 2-amino-3-nitrobenzoic acid, with a purity of 99%, Mp97~98°C (document Mp97~98°C),

Embodiment 3

[0067] Embodiment 3: Preparation of ethyl 2-amino-3-nitrobenzoate:

[0068] ①.Monoesterification (preparation of ethyl 2-carboxy-3-nitrobenzoate);

[0069] 500ml of absolute ethanol, 90g of 3-nitrophthalic acid, 50ml of concentrated sulfuric acid, heated to reflux, followed by liquid chromatography to control the end point of the reaction, cooling down to crystallize to obtain the monoesterification product: ethyl 2-carboxy-3-nitrobenzoate Ester, dried product 81.5g, purity 99.2%, Mp105.4~107℃ (document Mp105~108℃).

[0070] ②. Acyl chloride;

[0071] Add 200ml of chloroform and 45g of thionyl chloride to 81.5g of the monoesterification product (dried product), reflux reaction, and lower the temperature to obtain a solution of acid chloride.

[0072] ③.Curtius heavy discharge hydrolysis;

[0073] To the solution of acid chloride, add 30g of sodium azide, react at room temperature, follow and control the reaction end point by liquid chromatography, after the reaction is comp...

technical field

[0001] The invention relates to a preparation method of 2-amino-3-nitrobenzoic acid widely used in the synthesis and preparation of medicines, pesticides and various functional materials. Background technique

[0002] 2-Amino-3-nitrobenzoic acid is an important intermediate in organic synthesis, used in the synthesis of pesticides and various functional materials, and also in the synthesis of benzimidazole drugs candesartan, azilsartan, ABT- 472 Key intermediates of PAPR inhibitors.

[0003] The synthesis of 2-amino-3-nitrobenzoic acid, the relevant patent documents are as follows:

[0004] 1. U.S. patent: US2005 020 626, using 2-chloro-3-nitrobenzoic acid as raw material to obtain 2-amino-3-nitrobenzoic acid through ammonolysis.

[0005] 2. Japanese patent: JP2001 163 843, using 7-nitroisatin as raw material, undergoing oxidation and alkaline hydrolysis under alkaline conditions to obtain 2-amino-3-nitrobenzoic acid.

[0006] 3. There are public documents...

Examples

Embodiment 1

[0058] Embodiment 1: the preparation of 2-amino-3-nitrobenzoic acid methyl ester:

[0059] ①.Monoesterification (preparation of 2-carboxy-3-nitrobenzoic acid methyl ester);

[0060]600ml of anhydrous methanol, 100g of 3-nitrophthalic acid, 50ml of concentrated sulfuric acid, heated to reflux, followed by liquid chromatography to control the end point of the reaction, and crystallized at 0°C to obtain the monoesterification product: 2-carboxy-3-nitrobenzene Methyl formate, dried product 90.4g, purity 98.8%, Mp160.4~161℃ (document Mp160~162℃).

[0061] ②. Acyl chloride;

[0062] Add 300ml of chloroform and 50g of thionyl chloride to the monoesterification product (dried product), reflux reaction, and lower the temperature to obtain a solution of acid chloride.

[0063] ③.Curtius heavy discharge hydrolysis;

[0064] To the solution of acid chloride, add 35g of sodium azide, react at room temperature, follow and control the reaction end point by liquid chromatography, after the...

Embodiment 2

[0065] Embodiment 2: the preparation of 2-amino-3-nitrobenzoic acid:

[0066] Add 60g of methyl 2-amino-3-nitrobenzoate, add 300ml of water and 15g of sodium hydroxide, heat to reflux, follow the liquid chromatography to control the end point of the reaction, complete hydrolysis, lower the temperature, add hydrochloric acid dropwise, adjust the pH to 2-3, and crystallize on cooling , to get 54.5g of 2-amino-3-nitrobenzoic acid, with a purity of 99%, Mp97~98°C (document Mp97~98°C),

Embodiment 3

[0067] Embodiment 3: Preparation of ethyl 2-amino-3-nitrobenzoate:

[0068] ①.Monoesterification (preparation of ethyl 2-carboxy-3-nitrobenzoate);

[0069] 500ml of absolute ethanol, 90g of 3-nitrophthalic acid, 50ml of concentrated sulfuric acid, heated to reflux, followed by liquid chromatography to control the end point of the reaction, cooling down to crystallize to obtain the monoesterification product: ethyl 2-carboxy-3-nitrobenzoate Ester, dried product 81.5g, purity 99.2%, Mp105.4~107℃ (document Mp105~108℃).

[0070] ②. Acyl chloride;

[0071] Add 200ml of chloroform and 45g of thionyl chloride to 81.5g of the monoesterification product (dried product), reflux reaction, and lower the temperature to obtain a solution of acid chloride.

[0072] ③.Curtius heavy discharge hydrolysis;

[0073] To the solution of acid chloride, add 30g of sodium azide, react at room temperature, follow and control the reaction end point by liquid chromatography, after the reaction is comp...

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