CN110668968A - Preparation method of p-aminobenzoyl glutamic acid - Google Patents
Preparation method of p-aminobenzoyl glutamic acid Download PDFInfo
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- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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Abstract
The invention discloses a preparation method of p-aminobenzoyl glutamic acid, which comprises the following specific steps: adding nitrobenzoic acid, oxalyl chloride, dichloroethane and DMF (dimethyl formamide) into a reaction container to react to obtain paranitrobenzoyl chloride; reacting paranitrobenzoyl chloride with sodium glutamate to obtain paranitrobenzoyl glutamic acid; the p-nitrobenzoyl glutamic acid is subjected to unit processes of reduction, separation, acidification, refining and drying in the presence of a polar solvent and a catalyst to obtain a finished product, wherein the reduction is hydrogenation and hydrazine hydrate reduction after the pH is adjusted to 6-10 by sodium hydroxide. The method has the advantages of mild reaction, simple and convenient operation, high process safety, lower production cost, environmental protection, high purity and high yield of the obtained product, repeated use of the catalyst, recycling of the solvent after distillation and recovery, reaching the standard after alkali treatment of a small amount of waste liquid, and less environmental pollution, thereby being suitable for industrial production.
Description
Technical Field
The invention relates to a medical intermediate, in particular to a preparation method of p-aminobenzoyl glutamic acid.
Background
P-aminobenzoyl glutamic acid is a key intermediate for synthesizing folic acid. The pharmaceutical intermediates are chemical raw materials or chemical products used in the process of synthesizing the medicines, the chemical products can be produced in a common chemical plant without production licenses of the medicines, and can be used for synthesizing the medicines as long as the pharmaceutical intermediates reach certain levels, more than 2000 kinds of raw materials and intermediates matched with the chemical industry are required in China every year, the demand reaches more than 250 ten thousand tons, and after more than 30 years of development, the chemical raw materials and the intermediates required by the pharmaceutical production in China can be basically matched, only a small part of the chemical raw materials and the intermediates are required to be imported, and because resources in China are rich, the price of the raw materials is low, and a large amount of intermediates are exported.
The currently generally known process for preparing p-aminobenzoyl glutamic acid is as follows: taking p-nitrobenzoic acid as a starting material, preparing p-nitrobenzoyl chloride through acyl chlorination reaction, then carrying out condensation reaction with sodium glutamate, and reducing by iron powder to obtain the p-nitrobenzoyl chloride. The method has the advantages of low yield, long reaction time and environmental pollution caused by a large amount of waste residues (iron mud) and waste water, so the preparation method of the p-aminobenzoyl glutamic acid is provided to solve the problems.
Disclosure of Invention
The invention aims to provide a preparation method of p-aminobenzoyl glutamic acid with high yield and less environmental pollution, so as to solve the problems in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme:
a preparation method of p-aminobenzoyl glutamic acid comprises the following specific steps:
(1) weighing 10-15 parts of p-nitrobenzoic acid, 15-20 parts of oxalyl chloride, 10-14 parts of dichloroethane as a solvent and 50-60 parts of DMF, adding nitrobenzoic acid, oxalyl chloride, dichloroethane and DMF into a reaction vessel for reaction, heating the reaction vessel to 50-60 ℃, continuously heating for 1-2 hours, after the reaction is finished, putting the mixed reactant into a distillation vessel, slowly heating the distillation vessel in a water bath manner to control the temperature of the distillation vessel to be 80-100 ℃, distilling for 2-3 hours, and distilling through the distillation vessel to recover the solvent and remove hydrogen chloride to obtain p-nitrobenzoyl chloride;
(2) adding the obtained paranitrobenzoyl chloride into a reaction container, adding 12-16 parts of sodium glutamate and 45-65 parts of water, regulating the pH to 8-9 by using 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 0-5 ℃, regulating the pH value by using 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 8-9, reacting at room temperature for 1-3h after dropwise adding is finished, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, regulating the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain paranitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 6-10 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 1-3MPa, the using amount of hydrazine hydrate is 30-40 parts, and the reaction temperature is 80-120 ℃.
As a further scheme of the invention:
the polar solution is one or more of water, trifluoroacetic acid, acetic acid, triethylamine, methyl formate and ethyl acetate.
As a still further scheme of the invention:
the catalyst is ferric chloride hexahydrate.
Compared with the prior art, the invention has the beneficial effects that:
the method has the advantages of mild reaction, simple and convenient operation, high process safety, lower production cost, environmental protection, high purity and high yield of the obtained product, repeated use of the catalyst, recycling of the solvent after distillation and recovery, reaching the standard after alkali treatment of a small amount of waste liquid, and less environmental pollution, thereby being suitable for industrial production.
Detailed Description
The technical solution of the present patent will be described in further detail with reference to the following embodiments.
Example 1
A preparation method of p-aminobenzoyl glutamic acid comprises the following specific steps:
(1) weighing 10 parts of p-nitrobenzoic acid, 15 parts of oxalyl chloride, 10 parts of dichloroethane as a solvent and 50 parts of DMF, adding the nitrobenzoic acid, the oxalyl chloride, the dichloroethane and the DMF into a reaction vessel for reaction, heating the reaction vessel to 50 ℃, and continuously heating for 1h, wherein the reaction vessel needs to be capped during the heating process of the reaction vessel, and the inside of the reaction vessel is continuously stirred at a constant speed to ensure that the nitrobenzoic acid and thionyl chloride react uniformly; after the reaction is finished, putting the mixed reactant into a distillation container, slowly heating the distillation container in a water bath mode to control the temperature of the distillation container to be 80 ℃, distilling for 2 hours, and distilling through the distillation container to recover the solvent and remove hydrogen chloride to obtain the paranitrobenzoyl chloride;
(2) adding the obtained paranitrobenzoyl chloride into a reaction container, adding 12 parts of sodium glutamate and 45 parts of water, adjusting the pH to 8 by using 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 0 ℃, adjusting the pH value by using 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 8, reacting at room temperature for 1h after dropwise adding, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, adjusting the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain paranitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 6 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 1MPa, the consumption of hydrazine hydrate is 30 parts, and the reaction temperature is 80 ℃.
The appearance of the p-aminobenzoyl glutamic acid obtained by hydrogenation and hydrazine hydrate reduction in the method is a white-like crystal, the melting point is 168-171 ℃, the purity is 99.93 percent (HPLC), and the three-step yield is 96.8 percent based on p-nitrobenzoic acid.
Example 2
A preparation method of p-aminobenzoyl glutamic acid comprises the following specific steps:
(1) weighing 11 parts of p-nitrobenzoic acid, 16 parts of oxalyl chloride, 11 parts of dichloroethane as a solvent and 52 parts of DMF, adding the nitrobenzoic acid, the oxalyl chloride, the dichloroethane and the DMF into a reaction vessel for reaction, heating the reaction vessel to 52 ℃, and continuously heating for 1.2h, wherein in the heating process of the reaction vessel, the reaction vessel needs to be covered, and the interior of the reaction vessel is continuously stirred at a constant speed to ensure that the nitrobenzoic acid and thionyl chloride react uniformly; after the reaction is finished, putting the mixed reactant into a distillation container, slowly heating the distillation container in a water bath mode to control the temperature of the distillation container to be 85 ℃, distilling for 2.2 hours, and distilling through the distillation container to recover the solvent and remove hydrogen chloride to obtain paranitrobenzoyl chloride;
(2) adding the obtained p-nitrobenzoyl chloride into a reaction container, adding 13 parts of sodium glutamate and 50 parts of water, regulating the pH to 8.2 by using a 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 1 ℃, regulating the pH value by using a 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 8.2, reacting at room temperature for 1.5h after dropwise adding is finished, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, regulating the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain p-nitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 7 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 1.5MPa, the using amount of hydrazine hydrate is 32 parts, and the reaction temperature is 90 ℃.
The appearance of the p-aminobenzoyl glutamic acid obtained by hydrogenation and hydrazine hydrate reduction in the method is a white crystal, the melting point is 169-172 ℃, the purity is 99.94 percent (HPLC), and the three-step yield is 96.9 percent based on p-nitrobenzoic acid.
Example 3
A preparation method of p-aminobenzoyl glutamic acid comprises the following specific steps:
(1) weighing 12 parts of p-nitrobenzoic acid, 18 parts of oxalyl chloride, 12 parts of dichloroethane as a solvent and 55 parts of DMF, adding the nitrobenzoic acid, the oxalyl chloride, the dichloroethane and the DMF into a reaction vessel for reaction, heating the reaction vessel to 55 ℃, and continuously heating for 1.5h, wherein in the heating process of the reaction vessel, the reaction vessel needs to be covered, and the interior of the reaction vessel is continuously stirred at a constant speed to ensure that the nitrobenzoic acid and thionyl chloride react uniformly; after the reaction is finished, putting the mixed reactant into a distillation container, slowly heating the distillation container in a water bath mode to control the temperature of the distillation container to be 90 ℃, distilling for 2.5 hours, and distilling through the distillation container to recover the solvent and remove hydrogen chloride to obtain paranitrobenzoyl chloride;
(2) adding the obtained p-nitrobenzoyl chloride into a reaction container, adding 14 parts of sodium glutamate and 55 parts of water, regulating the pH to 8.5 by using a 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 3 ℃, regulating the pH value by using a 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 8.5, reacting at room temperature for 1-3h after dropwise adding is finished, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, regulating the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain p-nitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 8 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 1-3MPa, the dosage of hydrazine hydrate is 35 parts, and the reaction temperature is 100 ℃.
The appearance of the p-aminobenzoyl glutamic acid obtained by hydrogenation and hydrazine hydrate reduction in the method is a white-like crystal, the melting point is 170-172 ℃, the purity is 99.96 percent (HPLC), and the three-step yield is 97.1 percent based on p-nitrobenzoic acid.
Example 4
A preparation method of p-aminobenzoyl glutamic acid comprises the following specific steps:
(1) weighing 14 parts of p-nitrobenzoic acid, 19 parts of oxalyl chloride, 14 parts of dichloroethane as a solvent and 58 parts of DMF, adding the nitrobenzoic acid, the oxalyl chloride, the dichloroethane and the DMF into a reaction vessel for reaction, heating the reaction vessel to 58 ℃, and continuously heating for 1.8h, wherein in the heating process of the reaction vessel, the reaction vessel needs to be covered, and the interior of the reaction vessel is continuously stirred at a constant speed to ensure that the nitrobenzoic acid and thionyl chloride react uniformly; after the reaction is finished, putting the mixed reactant into a distillation container, slowly heating the distillation container in a water bath mode to control the temperature of the distillation container to be 95 ℃, distilling for 2.8 hours, and distilling through the distillation container to recover the solvent and remove hydrogen chloride to obtain paranitrobenzoyl chloride;
(2) adding the obtained p-nitrobenzoyl chloride into a reaction container, adding 15 parts of sodium glutamate and 60 parts of water, regulating the pH to 8.8 by using a 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 4 ℃, regulating the pH value by using a 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 8.8, reacting at room temperature for 2.5h after dropwise adding is finished, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, regulating the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain p-nitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 9 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 2.5MPa, the using amount of hydrazine hydrate is 38 parts, and the reaction temperature is 110 ℃.
The appearance of the p-aminobenzoyl glutamic acid obtained by hydrogenation and hydrazine hydrate reduction in the method is white-like crystal, the melting point is 170-.
Example 5
A preparation method of p-aminobenzoyl glutamic acid comprises the following specific steps:
(1) weighing 15 parts of p-nitrobenzoic acid, 20 parts of oxalyl chloride, 14 parts of dichloroethane as a solvent and 60 parts of DMF, adding the nitrobenzoic acid, the oxalyl chloride, the dichloroethane and the DMF into a reaction vessel for reaction, heating the reaction vessel to 60 ℃, and continuously heating for 2 hours, wherein the reaction vessel needs to be capped during the heating process of the reaction vessel, and the inside of the reaction vessel is continuously stirred at a constant speed to ensure that the nitrobenzoic acid and thionyl chloride react uniformly; after the reaction is finished, putting the mixed reactant into a distillation container, slowly heating the distillation container in a water bath mode to control the temperature of the distillation container to be 100 ℃, distilling for 3 hours, and distilling through the distillation container to recover the solvent and remove hydrogen chloride to obtain the paranitrobenzoyl chloride;
(2) adding the obtained paranitrobenzoyl chloride into a reaction container, adding 16 parts of sodium glutamate and 65 parts of water, adjusting the pH to 9 by using 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 5 ℃, adjusting the pH value by using 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 9, reacting at room temperature for 3 hours after dropwise adding, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, adjusting the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain paranitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 10 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 3MPa, the consumption of hydrazine hydrate is 40 parts, and the reaction temperature is 120 ℃.
The appearance of the p-aminobenzoyl glutamic acid obtained by hydrogenation and hydrazine hydrate reduction in the method is a white-like crystal, the melting point is 171-174 ℃, the purity is 99.95 percent (HPLC), and the three-step yield is 96.9 percent based on p-nitrobenzoic acid.
The polar solution is one or more of water, trifluoroacetic acid, acetic acid, triethylamine, methyl formate and ethyl acetate. The catalyst is ferric chloride hexahydrate.
The method has the advantages of mild reaction, simple and convenient operation, high process safety, lower production cost, environmental protection, high purity and high yield of the obtained product, repeated use of the catalyst, recycling of the solvent after distillation and recovery, reaching the standard after alkali treatment of a small amount of waste liquid, and less environmental pollution, thereby being suitable for industrial production.
Although the preferred embodiments of the present patent have been described in detail, the present patent is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present patent within the knowledge of those skilled in the art.
Claims (3)
1. The preparation method of p-aminobenzoyl glutamic acid is characterized by comprising the following specific steps:
(1) weighing 10-15 parts of p-nitrobenzoic acid, 15-20 parts of oxalyl chloride, 10-14 parts of dichloroethane as a solvent and 50-60 parts of DMF, adding nitrobenzoic acid, oxalyl chloride, dichloroethane and DMF into a reaction vessel for reaction, heating the reaction vessel to 50-60 ℃, continuously heating for 1-2 hours, after the reaction is finished, putting the mixed reactant into a distillation vessel, slowly heating the distillation vessel in a water bath manner to control the temperature of the distillation vessel to be 80-100 ℃, distilling for 2-3 hours, and distilling through the distillation vessel to recover the solvent and remove hydrogen chloride to obtain p-nitrobenzoyl chloride;
(2) adding the obtained paranitrobenzoyl chloride into a reaction container, adding 12-16 parts of sodium glutamate and 45-65 parts of water, regulating the pH to 8-9 by using 1mol/L sodium hydroxide aqueous solution under stirring, slowly dropwise adding an ammonium chloride solution at 0-5 ℃, regulating the pH value by using 1mol/L sodium hydroxide aqueous solution while dropwise adding, keeping the pH of a reaction system at 8-9, reacting at room temperature for 1-3h after dropwise adding is finished, standing and layering, extracting an organic layer for 2 times by using water, combining water layers, regulating the pH to 1 by using hydrochloric acid, separating out crystals, filtering and drying to obtain paranitrobenzoyl glutamic acid;
(3) the p-nitrobenzoyl glutamic acid is subjected to reduction, separation, acidification, refining and drying under the condition of polar solvent and catalyst to obtain a finished product, wherein the reduction is to adjust the pH to 6-10 by using sodium hydroxide and then carry out hydrogenation and hydrazine hydrate reduction, the hydrogen pressure is 1-3MPa, the using amount of hydrazine hydrate is 30-40 parts, and the reaction temperature is 80-120 ℃.
2. The method for preparing p-aminobenzoylglutamic acid according to claim 1, wherein the polar solution is one or more of water, trifluoroacetic acid, acetic acid, triethylamine, methyl formate, ethyl acetate.
3. The method for preparing p-aminobenzoylglutamic acid according to claim 1, wherein the catalyst is ferric chloride hexahydrate.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113651712A (en) * | 2021-08-17 | 2021-11-16 | 北京斯利安药业有限公司 | Method for preparing N-p-aminobenzoyl-L-glutamic acid |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1296943A (en) * | 2000-10-25 | 2001-05-30 | 安徽省科苑应用技术开发(集团)股份有限公司 | Process for preparing p-aminobenzoyl glutaminic acid by reducing p-nitrobenzoyl glutaminic acid |
CN104478751A (en) * | 2014-12-13 | 2015-04-01 | 常熟华港制药有限公司 | Preparation method of p-amino benzamide glutamic acid |
CN104744296A (en) * | 2013-12-26 | 2015-07-01 | 李磊 | Production method of balsalazide |
CN105439895A (en) * | 2015-12-30 | 2016-03-30 | 浙江汇能生物股份有限公司 | Preparation method of N (4-aminobenzoyl)-L-glutamic acid |
CN108147977A (en) * | 2017-12-27 | 2018-06-12 | 江苏尚莱特医药化工材料有限公司 | The preparation method of N- p-benzoyls-Pidolidone |
CN109053482A (en) * | 2018-09-27 | 2018-12-21 | 上海雅本化学有限公司 | A kind of preparation method of N- (4- aminobenzoyl)-Pidolidone |
-
2019
- 2019-09-24 CN CN201910903631.7A patent/CN110668968A/en active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1296943A (en) * | 2000-10-25 | 2001-05-30 | 安徽省科苑应用技术开发(集团)股份有限公司 | Process for preparing p-aminobenzoyl glutaminic acid by reducing p-nitrobenzoyl glutaminic acid |
CN104744296A (en) * | 2013-12-26 | 2015-07-01 | 李磊 | Production method of balsalazide |
CN104478751A (en) * | 2014-12-13 | 2015-04-01 | 常熟华港制药有限公司 | Preparation method of p-amino benzamide glutamic acid |
CN105439895A (en) * | 2015-12-30 | 2016-03-30 | 浙江汇能生物股份有限公司 | Preparation method of N (4-aminobenzoyl)-L-glutamic acid |
CN108147977A (en) * | 2017-12-27 | 2018-06-12 | 江苏尚莱特医药化工材料有限公司 | The preparation method of N- p-benzoyls-Pidolidone |
CN109053482A (en) * | 2018-09-27 | 2018-12-21 | 上海雅本化学有限公司 | A kind of preparation method of N- (4- aminobenzoyl)-Pidolidone |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113651712A (en) * | 2021-08-17 | 2021-11-16 | 北京斯利安药业有限公司 | Method for preparing N-p-aminobenzoyl-L-glutamic acid |
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